National Academies Press: OpenBook

Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program (2005)

Chapter: 4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry

« Previous: 3 Basic Concepts in Radiation Physics, Biology, and Epidemiology
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

4
Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry

The statement of task from the Health Resources and Services Administration (HRSA) to the committee requests that we assess the most recent scientific information related to radiation exposure and associated cancers to determine whether there is new information that could affect the magnitude of radiation cancer-risk estimates. If there is, it would provide part of the information base that is needed for considering the inclusion of new populations and new geographic areas in the Radiation Exposure Compensation Act (RECA) populations.

The risk estimates for human cancers after exposures to low-LET ionizing radiation are based on human tumor frequencies, which come mainly from cancer mortality data on the survivors of the atomic-bomb detonations at Hiroshima and Nagasaki (NRC, 1990; ICRP, 1991; NCRP, 2001; reviewed in Wakeford, 2004). Risk estimates for high-LET radiation are based on mortality data on uranium and other underground miners exposed to radon (NRC, 1999) and on the radium-dial painters (NRC, 1988; reviewed in Wakeford, 2004). The responses at very low exposures to low-LET radiation are estimated by extrapolation of data on atomic-bomb survivors over the available low- to moderate-dose range (0.005–2 Sv). The extrapolation model used is the linear nonthreshold (LNT) one (NCRP, 2001) that is discussed in Chapter 3. Support for the use of the LNT model for estimates of cancer risks posed by low-LET radiation comes from human epidemiologic studies (medical and occupational), experimental-animal tumor studies, and cellular-radiation studies (NCRP, 2001). The data from similar but fewer studies involving high-LET exposures support the use of the LNT model here also (NCRP, 2001). The same types of studies are used to provide estimates of the effects of dose fractionation and dose protraction (NCRP, 2001). Epidemio-

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

logic studies are also used for estimating risks to specific exposed populations, such as underground miners exposed to radon (NRC, 1999) and populations exposed to iodine-131 (131I) (UNSCEAR, 2000).

The International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP) are moving to use tumor incidence, rather than mortality, in their revised cancer risk estimates. Using tumor-incidence data for developing risk estimates provides an additional useful measure of risk because morbidity entails health, emotional, and financial costs to the individual and society.

In this chapter, we consider and present the evidence from new or updated epidemiologic studies, radiation-biology advances, or dosimetry approaches that could result in significant changes in the risk estimates for human cancer induced by ionizing-radiation exposure. This chapter brings together information that could influence compensation for diseases currently covered by RECA legislation. In Chapter 7, we discuss additional diseases brought to our attention by members of the public at a series of hearings held in response to community invitations with a view to whether eligibility for coverage should be extended thereto. The following sections discuss what is new in those fields of study.

RECENT DEVELOPMENTS IN RADIATION EPIDEMIOLOGY

Epidemiologic studies of the Japanese survivors of the atomic bombs and of other populations exposed to radiation medically, occupationally, or accidentally have characterized the long-term health effects of radiation (see Chapter 3). Risks estimates for radiogenic cancers and nonmalignant diseases now compensable under RECA come primarily from epidemiologic studies of uranium and other underground miners exposed to radon and from studies of the atomic-bomb survivors. The mining populations were exposed primarily to radon internally while the atomic-bomb survivors were exposed primarily to external gamma rays. Risk estimates for thyroid cancer also come from populations exposed to external x and gamma rays, and internally to radioiodine. Studies of worker populations exposed to low or very low doses of low LET radiations over long periods provide radiogenic-cancer risk estimates with which the more precise estimates obtained from the atomic-bomb survivors can be compared to evaluate their applicability to populations chronically exposed to low radiation levels. Extensive and detailed reviews of those studies have been reported previously (NRC, 1990, 1998; 1999; ICRP, 1991; UNSCEAR, 1993, 2000; IARC, 2000; 2001).

A comprehensive reassessment of risk estimates is included in a companion, forthcoming report from the National Research Council Committee on Biological Effects of Ionizing Radiation (BEIR) specifically, the Committee on Health Risks from Exposure to Low Levels of Ionizing Radiation (BEIR VII).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

Risks to the Health of Miners, Millers, and Ore Transporters

Studies of Uranium Miners

Epidemiologic studies of underground miners have identified an increased risk of primary lung cancer associated with exposure to alpha-particle radiation from decay products of inhaled radon (NRC, 1988). Those studies generally need relative-risk (RR) models; estimates are discussed below. Although absolute risk is important from a public-health perspective, we choose to discuss RR and excess relative risk (ERR; ERR = RR − 1) because of their use in the cited literature.

The most recent and widely recognized lung-cancer risk estimates associated with radon exposure were reported in the BEIR VI report (NRC, 1999). An important finding of the BEIR VI committee relevant to some of the RECA populations—identified as uranium miners, uranium millers, and ore transporters—is that the ERR of radiogenic lung cancer decreases with increasing attained age and time since exposure. The eligible people now seeking compensation are generally more than 60 years old and have been out of the mines for 30 years or more. Accordingly, they are at much lower RR for radiogenic lung cancer now than they were in earlier years after retiring from mining uranium. Using data on 11 international cohorts, the BEIR VI committee estimated that uranium miners 65-74 years old have about 25% of the ERR of radon-induced lung cancer that miners in their 50s have. The most recent analysis of the Colorado Plateau uranium-miner data (Hornung et al., 1998) estimated that the ERR for lung cancer in miners in their 70s was less than 10% of that of miners in their 50s. Similarly, the BEIR VI committee estimated that miners of the same age who have been out of the mines for more than 25 years have less than half the lung-cancer ERR of recently retired miners. The analysis of the Colorado Plateau miner lung-cancer data indicated a 65% reduction in ERR for miners who have been out of the mines for more than 25 years.

Those analyses also have shown a synergistic relationship between exposure to radon and cigarette smoking. That is, the ERR of radiogenic lung cancer in smoking miners is greater than the sum of the ERRs of lung cancer associated with smoking alone and radon alone. The most recent analysis of the Colorado Plateau uranium miners cohort (Hornung et al., 1998) and the pooled analysis of 11 miner cohorts in BEIR VI (NRC, 1999) each found that the joint effect was greater than additive but less than multiplicative. The nature of the interaction was that never-smokers had about 3 times the ERR per WLM of ever-smokers in both analyses. These findings were supported by a study of non-smoking uranium miners in the Colorado Plateau (Roscoe, 1997) who had an SMR = 12.7 for lung cancer compared with the overall SMR = 5.8 in the entire cohort.

In the most recent update of all cancer mortality in the Colorado Plateau uranium miners’ all-cause mortality study (Roscoe, 1997), the cohort of 3,238

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

white male miners was followed to determine certified causes of deaths in 1960-1990. Their mortality experience was compared with the combined mortality in neighboring states. Most of the findings of the study were consistent with those of previous studies of this miner population. The standardized mortality ratios (SMRs) for lung cancer and pneumoconiosis continued to show statistically significant increases (371 deaths, SMR = 5.8, 95% CI [confidence interval] = 5.2-6.4 and 41 deaths, SMR = 24.1, 95% CI = 16.0-33.7, respectively). The SMRs for lung cancer and pneumoconiosis increased with increasing level of radon-decay products and with duration of employment in the mines. Roscoe (1997) concluded that lung cancer and pneumoconiosis remain the most important long-term causes of death in this cohort.

The most definitive study of cancer other than lung cancer among miners exposed to radon was the meta-analysis of data on the 11 international miner cohorts reported by Darby et al. (1995). The men in those cohorts (N = 64,209) had been employed in underground mines for an average of 6.4 years; they had an estimated average annual cumulative exposure to radon of 155 working-level months (WLM) and an average followup of almost 17 years. The RR of all cancer causes of death combined other than lung cancer (N = 1,179) was similar to the expected value (RR = 1.01, 95% CI = 0.95-1.07), on the basis of the mortality of the general populations in areas around the mines. Those results should be interpreted cautiously since they are likely to underestimate the true RR in the uranium miner population due to the Healthy Worker Effect. The authors concluded that the study provided strong evidence that high concentrations of radon in air do not cause a substantial risk of mortality from cancer other than lung cancer.

Studies of Uranium Millers and Ore Transporters

Risks to the health of uranium millers and ore transporters from occupational exposure have not been as well characterized as the risks to miners’ health because of smaller sample sizes and little or no data on individual exposures. Exposures to millers were primarily from inhalation of dusts containing uranium, silica, and vanadium. Their internal exposure posed potential health hazards from radiation (alpha particles) and from the chemical toxicity of uranium compounds arising during the conversion of uranium ore to yellow cake (see Chapter 3).

A study of mortality among 662 millers from the Colorado Plateau who were followed from 1950 through 1967 (Archer et al., 1973) found four deaths from lymphatic and hematopoietic cancers combined (excluding leukemia), for a small and nonstatistically significant increase over the rate in the US general population. A later larger and more powerful study evaluated mortality among an expanded cohort of millers in the same area (N = 2,002) who were followed through 1971 (Waxweiler et al., 1983). They found no statistically significantly

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

increased RRs of mortality from any malignant (radiogenic or other) neoplasm, including renal cancer. The only statistically significant increase in disease risk in that cohort was for nonmalignant respiratory disease (55 deaths, SMR = 1.63, 95% CI = 1.23-2.12); however, there was no evidence that the risk increased with increasing length of employment. A nonstatistically significant ERR of death from chronic (nonmalignant) renal disease (6 deaths; SMR = 1.67, 95% CI = 0.60-3.5) was also found, but it did not appear to be related to work in the mills.

Pinkerton et al. (2004) updated the Waxweiler et al. study by extending the vital-status followup by 27 years December 31, 1998. The authors completely reviewed and updated all work histories and recoded errors found in previous files. They also limited the study cohort to men who met the original cohort definition, never worked in uranium mines, and worked in one or more of seven mills whose personnel records were originally microfilmed. That redefinition of the study cohort resulted in a reduction in the size of the cohort from 2,002 in the Waxweiler et al. study to 1,485. Because exposure estimates were not available for individual workers, Pinkerton et al. used life-table analyses to compare mortality in the workers with that in the general US population.

Mortality from all causes combined (810 deaths, SMR = 0.92, 95% CI = 0.86-0.99), including all cancers (184 cancer deaths observed, SMR = 0.90, 95% CI = 0.78-1.04), was less than expected on the basis of US rates. A statistically significant increase in nonmalignant respiratory disease mortality was found (100 deaths, SMR = 1.43, 95% CI = 1.16-1.73). No statistically significant increase was found in mortality from lung cancer (78 deaths, SMR = 1.13, 95% CI = 0.89-2.35) or chronic renal disease (6 deaths, SMR = 1.35, 95% CI = 0.58-2.67). No positive trend in excess mortality from these or any other types of cancer with duration of employment was found.

There have been few studies of morbidity among uranium millers. Thun and colleagues examined renal toxicity in a group of 39 uranium millers compared with 36 cement-plant workers (Thun et al., 1985). They found a weak dose-response relationship for excretion of beta-2-microglobulin among millers working in the yellowcake drying and packaging area, the area with the highest exposure to soluble uranium. They concluded that the results suggested reabsorbtion of low-molecular-weight proteins consistent with uranium nephrotoxicity.

More recently there have been two studies of uranium workers that were engaged in production activities using the uranium coming from the mills. A study of uranium enrichment workers (McGeoghegan and Binks, 2000a) in the UK found no overall excess mortality or morbidity due to any cancer when compared to non-radiation workers. They did find, however, a significant dose-response relationship for bladder cancer when external radiation dose was lagged by 20 years. A similar study by the same investigators regarding workers involved in the production of nuclear fuels and uranium hexafluoride (McGeoghegan and Binks, 2000b) found no significant association of radiation exposure and any cancer with the exception of Hodgkin’s disease (both mortality and morbidity).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

They also reported a significant association with morbidity due to nonHodgkin’s lymphoma. They noted that these associations were not likely to be causal.

The committee is unaware of any epidemiologic studies of ore transporters. Like the millers’ exposure, their primary potentially hazardous exposure was to ore dusts, probably with a greater risk of chemical toxicity than radiation toxicity. The nature of their work makes it unlikely that their body burdens of soluble uranium compounds exceeded renal thresholds for chemical toxicity or that their exposure to radiation from the ores substantially exceeded normal background levels.

Risks to Downwinders and Onsite Participants at US Nuclear Tests

Several populations have been at risk of exposure to ionizing radiation of types similar to those of downwinders and onsite test participants. Followup studies of the other populations provide information about the long-term health effects of such exposure; some also provide data from which estimates of the risks of radiation-related or radiogenic diseases, primarily malignant diseases, are calculated. We discuss here new information from specific population studies that adds to the knowledge and understanding of the types and magnitude of the health risks for which downwinders and onsite test participants currently are compensated.

Radiogenic Cancers and Other Diseases

Information on radiation risks is summarized in many of cited sources (UNSCEAR, NRC, and NCRP) and chapters in several textbooks dealing with the subject (Mettler and Upton, 1995; Hall, 2000). Updated information is scheduled to appear shortly in a report from the BEIR VII committee. The risk estimates in BEIR VII take into account DS02 data for the atomic-bomb survivors that were not available to this committee, and those data should be used whenever there are significant discrepancies between findings we survey from literature published in the last 20 years, and the BEIR VII update based on reanalysis of current data. Long-term studies of irradiated populations continue to provide new information on effects from internal and external sources of exposure. Effects of high-dose-rate exposure are chronicled in reports of findings in the Japanese atomic-bomb survivors supplemented by data from several large studies of radiation workers exposed to low-dose-rate radiation. The lower dose-rate exposures received by worker populations, along with data from medical-therapy populations add to the current status of knowledge of the risks in humans of the different radiogenic diseases with respect to rate and amount of radiation dose to body organs and the total body.

Dose from internal emitters is protracted because it is delivered over the decay time of the particular radionuclide. Effects of internal emitters of low

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

linear energy transfer (low LET) are less than those of comparable doses delivered in a single high-dose-rate exposure, because there is continuing repair of sublethal damage when a dose is delivered at a low dose rate. The need to expand knowledge of radiation effects of 131I has led to many studies, some of which continue. The dose to the thyroid from 131I per unit intake is about 1,000 times higher than the dose received by other normal organs. The dose to different body organs from other fallout radionuclides is much lower because of low uptake and retention in different organs (CDC-NCI, 2001). Increased incidence of thyroid cancer has been observed in children who received high 131I doses, but no increase in leukemia from the lower bone marrow doses received following 131I doses from fallout has been statistically confirmed. Continuing studies of health effects in persons resident in Southern Utah during the high NTS fallout years reveal marginally significant increases in thyroid neoplasms and leukemia in children.

The studies of disease in the Japanese atomic-bomb survivors provide the most reliable information for risk assessment for several reasons:

  • They received a wide range of dose; and, unlike medical subjects, the population is composed of people with a typical range of health conditions prior to their exposure.

  • Large numbers of subjects in well-defined cohorts have been studied over many years. Very good followup involving a range of ages and both sexes has resulted in many person-years of followup which is needed for valid statistical analyses.

  • Good estimates of dose have been calculated for each member of the cohort as a result of in-depth dosimetry studies (Dosimetry System 02, DS02). The new dosimetry system recently introduced incorporates refinements taking into account shielding histories and new information on neutrons (Preston et al., 2004; DS02 to be published in 2005).

Periodic publications update findings from the joint US-Japanese Radiation Effects Research Foundation studies of the several a priori-defined cohorts and subcohorts of the survivors of the atomic bombs dropped in 1945. The best established information on cancer mortality and cancer incidence comes from the large Life Span Study (LSS) cohort, buttressed by results of special studies of cancer in children born of irradiated parents (Izumi et al., 2003), and of leukemia mortality in children who were in utero at the time of the bombs (Delongchamp et al., 1997). In the absence of statistically meaningful data from fallout-exposed populations themselves, risk estimates from the atomic-bomb survivors are the best data we have to assess the magnitude and kinds of effects expected in downwinders and onsite test participants. Thyroid cancer is discussed in a separate section, which compares the results of studies in different irradiated populations.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

Atomic-Bomb Survivor Studies

Important cancer-mortality findings reported since 1990 and the results of new incidence studies are summarized below.


Cancer Mortality Cancer mortality through 1990 was analyzed on the basis of the DS86 dosimetry system. The major findings include

  • Most of the excess deaths from leukemia occurred in the first 15 years after exposure.

  • For solid cancers, the excess risk was consistent with a life-long increase in age-specific cancer risk.

  • The excess relative lifetime risk per sievert for solid cancers in persons exposed at the age of 30 was about three times greater than for persons exposed at age 50, and the projected lifetime risks for those exposed at age 10 were 1.0 to 1.8 times higher than the estimates for those exposed at age of 30 years.

  • Excess risks of solid cancers were linear up to about 3 Sv, but they were nonlinear for leukemia, for an estimated risk at 0.1 Sv of about 1/20 the risk at 1.0 Sv (Pierce et al., 1996).

More recently, the findings were extended through 1997 (Preston et al., 2003). The study included 9,335 deaths from solid cancer and 31,881 deaths from noncancer diseases on the basis of a 47-year followup. About 440 (5%) of the solid-cancer deaths were attributed to the radiation exposure. The excess risks of solid cancer were linearly related to dose down to the lowest dose studied (0-150 mSv). Results demonstrated that ERRs declined with increasing attained age (age at death); another was that the ERR was highest for those exposed as children. There was no direct evidence of radiation effects after doses less than about 0.5 Sv (Preston et al., 2003).


Cancer Incidence Cancer incidence in the atomic-bomb survivors is based on data in the Hiroshima and Nagasaki tumor registries.

Among 79,972 individuals in the extended Life Span Study (LSS-E85), 8,613 had a first primary solid cancer diagnosed between 1958 and 1987 (Thompson et al., 1994). Cancer cases occurring among members of the LSS-E85 cohort were identified in the Hiroshima and Nagasaki tumor registries and special efforts were made to ensure complete case ascertainment, data quality, and data consistency in the two cities. Dosimetry System 1986 (DS86) organ doses were used for computing risk estimates.

Ron et al. (1994) compared results from an analysis of 9,014 first primary incident cancers diagnosed in 1958-1987 in LSS cohort members and compared incidence with mortality rates based on analysis of 7,308 death certificates that listed cancer as the underlying cause of death. When deaths were limited to those

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

occurring in the same interval in persons living in Hiroshima or Nagasaki, there were 3,155 more incident cancer cases than cancer deaths overall and 1,262 more incident cancers of the digestive system than deaths from cancers of this system. For many cancers, the incidence series was at least twice as large as the comparable mortality series, and both had significant dose-response relationships. For all solid tumors, the estimated ERR at 1 Sv (ERR1Sv) for incidence (ERR1Sv = 0.63) is 40% larger than the ERR based on mortality data from 1950-1987 in all of Japan (ERR1Sv = 0.45). The corresponding excess absolute risk (EAR) point estimate is 2.7 times greater for incidence than for mortality. For some cancer sites, the difference in the magnitude of risk between incidence and mortality is greater. The differences reflect the greater diagnostic accuracy of the incidence data and the lack of full representation of radiosensitive but relatively nonfatal cancer, such as breast, skin, and thyroid cancers—in the mortality data. Incidence and mortality data provide complementary information for risk assessment (Ron et al., 1994).

The observations made in the tumor-registry studies are summarized in Table 4.1.

A survey of breast-cancer incidence in the LSS population found 1,093 breast cancers diagnosed during 1950-1990. A linear and statistically highly significant radiation dose-response relationship was found. Exposure before the age of 20 years was associated with higher ERR1Sv than exposure at greater ages, with no evidence of consistent variation with age of exposure for ages under 20 years. ERR1Sv was observed to decline with increasing attained age, with the largest drop around the age of 35 years (Land et al., 2003). The EAR was not reported, but it probably changed in the opposite direction, but to a lesser extent.

The incidence of leukemia, lymphoma, and myeloma in the LSS cohort from late 1950 through the end of 1987 was analyzed on the basis of followup of

TABLE 4.1 Tumor Incidence Rates Observed in the Japanese Atomic-Bomb Survivors (1994)

Thompson et al., 1994

ERR1Sv

EAR 10−4 PY Sv

Ron et al., 1994

ERR1Sv

All solid cancer

0.63

29.7

Significant increased risk

0.63

Stomach

0.32

 

Significant increased risk

 

Colon

0.72

Significant increased risk

Lung

0.95

Significant increased risk

Breast

1.59

Significant increased risk

Ovary

0.99

Significant increased risk

Urinary bladder

1.02

Significant increased risk

Thyroid

1.15

Significant increased risk

Liver

0.49

Significant increased risk

Nonmelanoma skin

1.0

Not stated

Salivary gland

 

Significant increased risk

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

93,696 survivors accounting for 2,778,000 PY (Preston et al., 1994). The analyses added 9 years of followup for leukemia and 12 years for myeloma to previous reports, and included the first analysis of lymphoma incidence in this cohort. The leukemia registry and the Hiroshima and Nagasaki tumor registries, included a total of 290 leukemia, 229 lymphoma, and 73 myeloma. The primary analyses were restricted to first primary tumors diagnosed among residents of the cities or surrounding areas with DS86 dose estimates of 0 - 4 Gy (231 leukemia, 208 lymphoma, and 62 myeloma) and used time-dependent models for the EAR. Separate analyses were reported for acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelocytic leukemia (CML), and adult T-cell leukemia/lymphoma (ATL). There were few cases of chronic lymphocytic leukemia (CLL) in the Japanese population independent of radiation exposure, so CLL was excluded from later leukemia risk analyses. There was strong evidence of radiation-induced risks for all subtypes except ATL, and there were substantial subtype differences with respect to the effects of sex and age at exposure and in the temporal pattern of risk. The AML dose-response function was nonlinear, whereas there was no evidence against linearity for the other subtypes. When averaged over the followup period, the EAR estimates (in cases per 104 PY Sv) were 0.6, 1.1, and 0.9 for ALL, AML, and CML, respectively. The corresponding estimated average ERRs at 1 Sv are 9.1, 3.3, and 6.2 respectively. There was some evidence of an increased risk of lymphoma in males (EAR = 0.6 case per 104 PY Sv) but no evidence of any excess in females. There was no evidence of an excess risk of multiple myeloma in these analyses.

Mortality from Leukemia and Solid Cancers in Children Exposed in Utero

Cancer mortality through 1992 was assessed in 807 atomic-bomb survivors exposed in utero and in 5,545 survivors who were less than 6 years old at time of exposure (Delongchamp et al., 1997). Doses in both groups were at least 0.01 Sv. Mortality was compared with that in low-dose group (10,453 persons with little or no exposure). Ten cancer deaths were observed among in utero-exposed persons, with a statistically significant dose-response relationship and an ERR per sievert of 2.1 (90% CI = 0.2-6.0). That estimate did not differ substantially from that for survivors exposed during the first 5 years of life. The cancer deaths among those exposed in utero included leukemia (two), female-specific organs (three), and digestive organs (five). Nine of the deaths occurred in females (ERR/Sv = 6.7, 90% CI = 1.6-17), and much of the effect was due to female-specific cancers (ERR/Sv = 9.7, 90% CI = 0.7-42). Those risks did not differ significantly from those seen in females exposed as children. No deaths from solid cancer occurred in males exposed in utero. Mortality in males and females differed even when female-specific cancers were excluded from the comparison. There were only two leukemia deaths among those exposed in utero, but the leukemia death

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

rate in this group was still marginally higher than in the comparison group (p = 0.054). The authors expressed caution in the interpretation of the data because of the number of cancer deaths was small, and because of the unexplained difference in mortality from solid cancer between sexes (Delongchamp et al., 1997). Their tentative conclusions were that the study provided support for a somewhat higher risk during the first trimester of pregnancy, that the increased risk persisted through childhood into the adult years, and that the pattern of diseases was similar after in utero and childhood exposure. Because of the wide uncertainty range, they concluded that their data did not exclude the possibility that the cancer risk from in utero exposures could be several times higher than the risk from childhood exposure.

A comprehensive review of the uncertainties contained in the different published studies is provided by Boice and Miller (1999). They discuss the confounding of reasons for referral with the risk of pelvimetry and conclude that “although it is likely that in utero radiation presents a leukemia risk to the fetus, the magnitude of the risk remains uncertain.” They found the causal nature of the risk of cancers other than leukemia to be less convincing, and the similar relative risk (RR = 1.5) for virtually all forms of childhood cancer suggested an underlying bias. Chapter 8 in Mettler and Upton (1995) also provides a broad review of current knowledge regarding the effects of radiation exposure in utero.

Conclusion Continuing investigations in the Japanese atomic-bomb survivors confirm and extend the evidence defining cancer mortality and risk after total-body high-dose-rate exposure. The radiation risk is better defined than previously based on the analysis of the incidence data classified by types of cancer, by age and sex at time of exposure. The high risk from thyroid cancer in children is consistent with the results of other studies (see thyroid cancer section). Data on cancer incidence and mortality from ongoing studies of the youngest survivors, all of whom are now over 60 years old, will be important as they emerge from studies. Although the risk of particular cancers posed by radiation is better described by incidence than by mortality, the number of documented cases in each disease category are still small, so the uncertainty range is wide. Continuing followup will be needed to increase confidence in disease-specific risk coefficients. The newest risk estimates are based on longer followup and better dosimetry.

Thyroid Cancer

Thyroid cancer is a relatively rare disease, with about 1,000 deaths certified and about 13 times as many new thyroid cancers reported each year in the United States (http://seer.cancer.gov/csr/1973_1998/thyroid.pdf, accessed February 17, 2005). A definite trend of increasing thyroid-cancer incidence during most of the last 60 years has been attributed in part to radiation therapy of the head and neck

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

given for benign conditions, a practice that has been discontinued since the 1950s and 1960s. Despite the increased incidence, primarily of the relatively benign papillary form of the disease, thyroid-cancer mortality declined in most of the ensuing years. In recent years, the upward trend has been influenced by increased case-finding brought about by routine use of ultrasonographic imaging of the thyroid. There are excellent reviews of the subject, including NCRP (1985, 1991, and 2001); ICRP (1991); UNSCEAR (1994 and 2000); Chapter 5, Thyroid Cancer section, in Mettler and Upton (1995); Shore et al., (1993); and Thomas et al., (1999).

New information since RECA was enacted in 1990 reveals a wider geographic distribution of dose from 131I than was generally recognized when Congress identified selected counties as affected areas for downwinder eligibility. It is now known that persons living in other states and in other counties in Utah could have received as high or higher thyroid doses as did those living in areas specified in RECA (NRC, 2003c). Recognition by the public of disparities in compensation created a need for further consideration of risk to the health of persons in the affected areas posed by fallout. The following text reviews the current state of knowledge concerning the risk of thyroid cancer after exposure to radiation from fallout and other sources of radiation exposure of the head and neck. For information on the distribution of dose from Nevada Test Site (NTS) weapons tests to the US population, see Figures 4.1-4.4.

Studies of Populations Exposed to Fallout from Nuclear-Test Releases

Fallout from Nevada Test Site

Several epidemiologic studies of Utah schoolchildren exposed to fallout from the NTS weapons tests have been conducted. The first showed no increase in thyroid disease (Rallison et al., 1974). A second followup study found a marginally significant increase when thyroid cancer was grouped together with benign thyroid nodules (Rallison et al., 1990). The 1990 cohort study compared the prevalence of thyroid abnormalities in children born between 1947 and 1954 who lived near the NTS in two counties, one in Utah and the other in Nevada, with a group selected from an Arizona county that was presumed to have had little or no fallout from the NTS.

Thyroid nodules were found in 76 of the 4,818 children examined (15.8/1,000). Of the 76 thyroid nodules, 22 were diagnosed as neoplasms. The rate of thyroid neoplasm in the Utah-Nevada cohort (5.6/1,000) was higher than the rate observed in the Arizona subjects (3.3/1,000) (RR = 1.7), but the difference was not statistically significant. In a 1985-1986 re-examination of the original study subjects, thyroid nodules were found in 125 people (44.2/1,000), and 65 were classified as neoplasms (benign and malignant). The rate of thyroid neoplasm in the Utah-Nevada cohort (24.6/1,000) was again slightly higher than in Arizona

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

cohort (20.2/1,000) (RR = 1.2), but the difference was not statistically significant (p = 0.65) (Rallison et al., 1990).

A third study (Kerber et al., 1993), estimated individual radiation doses and current thyroid-disease status in members of the same cohort of 4,818 schoolchildren studied by Rallison et al. The investigators collected questionnaire data on dietary intake during the fallout period and estimated thyroid doses from 131I for 2,473 of the subjects. RR models adjusted for age, sex, and location (state) were used to estimate prevalence data on thyroid carcinomas, benign neoplasms, and nodules. Doses ranged from 0 to 4,600 mGy, and averaged 170 mGy in Utah. There was a statistically significant excess of thyroid neoplasms (benign and malignant; n = 19) and an increase in ERR of 0.7% per mGy. A relative risk of thyroid neoplasia of 3.4 was observed among 169 subjects exposed to doses greater than 400 mGy. Positive but nonsignificant dose-response slopes were found for thyroid carcinomas and nodules (Kerber et al., 1993).

The only other cancer for which an increase attributed to NTS releases has been suggested is leukemia (not including CLL). Early studies by Lyon et al. (1979) and Machado (1987) posited an increase, but statistical evidence failed to support a significant dose-response relationship (Stevens et al., 1990). However, they did find a statistically significant association between leukemia and dose for those who died at age 20 and those dying in the period 1952-1957, which is surprisingly early, given the distribution for latent periods for nonCLL leukemia observed in the atomic-bomb survivors. The median dose for all subjects was 3.2 mGy (Simon et al., 1995). When all subjects were included weak but nonstatistically significant dose relationship was found (Gilbert et al., 2002). The most important source of radiation dose to the bone marrow is not 131I taken into the body, but external exposure to sources of radiation deposited on the ground (Beck and Krey, 1983). The maximum dose (internal and external) to the bone marrow from NTS fallout was estimated to be 3 - 10 mGy (see Figures 5.3 and 5.4 and the draft feasibility study of Bouville et al., 2002). The leukemia doubling dose was estimated at 1.1 Sv (EPA, 1999). There is no evidence to support a statistically significant increase in leukemia or any other cancer besides thyroid cancer from NTS releases in the heavily exposed southern Utah downwinders. It is unlikely that an increased incidence of leukemia or cancer, other than possibly thyroid cancer, from NTS fallout in residents exposed to comparable or lower doses in more distant locations in the United States would be detectable.

Marshall Island Studies

The Marshall Islanders resident on Rongelap and Utirik atolls received much larger doses than those exposed to NTS fallout, largely from the BRAVO test, one of the series of tests conducted by the United States at the Bikini atoll. The population has been under study since 1954. The Rongelap population received the highest thyroid dose, with estimates as high as 52 Gy in a 1 year old child, and

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

as high as 13 Gy in an adult female. An adult cancer patient on Utirik had an estimated thyroid dose of 6.8 Gy. The thyroid dose was 85% from short-lived radionuclides of iodine, and about 15% of the dose was from 131I. Thus, the type of exposure differed substantially in amount and kind from that experienced by the population living near the Nevada Test Site. Medical followup of the most heavily irradiated residents of Rongelap and Utirik was conducted by the Department of Energy and its predecessors through 1991 (Howard et al., 1997). These studies are reported in a series from the Brookhaven National Laboratory (BNL) (Howard et al., 1995, and Howard et al., 1997). A special issue of Health Physics (volume 73, 1997) was devoted to a review of the health consequences of nuclear testing in the Marshall Islands. Subsequent followup has been conducted by other international teams.

The small size of the group exposed on Rongelap and Utirik, the low fraction of the thyroid dose from 131I, uncertainties in the dosimetry, the intermittent use of thyroxin suppression after 1965, and the absence of ultrasound screening prior to 1994, taken together diminish the credibility of numerical risk estimates drawn from these studies. Thyroid nodules were first detected by palpation in 1963. Adenomatous nodules in Rongelap (17/67) and Utirik (10/167) were diagnosed and treated surgically. Of the 12 individuals exposed in utero (4 in Rongelap, and 8 in Utirik), 3 (12%) were found to have thyroid nodules, and 1 had a suspect papillary thyroid cancer. Most of the adenomatous nodules occurred in children under age 15 in Rongelap, with a risk estimated at 0.83 per 104 persons per mGy per year. There were 6 thyroid cancers diagnosed among the Rongelap exposed (7.0%), and 11 in the Utirik exposed (6.6%); 7 of the 17 cancers were classified as occult (microscopic) papillary cancers. Risk was estimated at 0.15 per 104 persons per mGy per year. The ratio of benign to malignant disease in the Utirik population was 3.5:1 in person’s age < 10 years at time of exposure (ATE), and 6.5:1 in those > 10 years ATE. In Rongelap exposed persons over age 10 years ATE, the benign to malignant ratio of nodules was 18:1. This suggested a smaller cancer risk when the thyroid dose exceeded 20 Gy, a decline that was presumed to be due to cell killing (Howard et al., 1997, NRC, 2000).

Marshallese living on the many atolls which comprise the Republic of the Marshall Islands (RMI) were exposed to a wide range of levels of fallout from the many tests at Bikini. A 10-year study examined 7,172 Marshallese (1993-1997) Takahashi et al., 2001. The investigators estimated thyroid dose based on recorded data for Utirik exposed individuals, but used 137Cs levels on the soil as a surrogate for estimating dose from 131I to the persons living on the other atolls. Exposed individuals in Rongelap were excluded in order to avoid non-linearity noted due to cell killing at the higher dose levels. They used ultrasound in their investigations and found 38 new thyroid cancers adding to the 30 reported previously. Summing over all the histological types, papillary variants comprised 77% of the 68 thyroid cancers with an additional 13% not classified as to cell type. Thyroid cancer was approximately twice as frequent in females as males.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

TABLE 4.2 Risk Factors of Thyroid Cancer Among 3,378 People Alive at the BRAVO Test for Whom Dose Estimates Could Be Deriveda

Weighted Median Dose (cGy)

Number of cases of thyroid cancer (%)

Adjusted Odds Ratio (for Total) (95% CI)

Male

Female

Total

0–3.4 (2.33)

3 (0.7)

8 (1.9)

11 (1.3)

1.0

3.4–7.5 (5.6)

6 (1.3)

4 (1.1)

10 (1.2)

0.99 (0.41-2.42)

7.5–18.7 (10.2)

2 (0.6)

12 (2.4)

14 (1.7)

1.37 (0.59-3.14)

18.7–677.7 (77)

4 (1.0)

11 (2.5)

15 (1.8)

1.67 (0.73-3.83)

aSOURCE: Adapted from Takahashi et al., 2001.

The absolute risk of thyroid cancer was not higher in persons exposed as children than as adults, but they were unable to correct analytically for temporal differences in ascertainment. Thyroid cancer risk was not significantly correlated with dose in 3,378 people for whom dose estimates could be made. Odds ratios were greater than 1.0 for the two highest dose quartiles, but the trend was not statistically significant (p = 0.15). The odds ratio for sex (female/male) was strongly positive, 2.11 (1.14-3.89) (See Table 4.2)

Clinical study findings approximately 40 years after the BRAVO test indicated that

  • Disorders of thyroid function, such as hypothyroidism and Graves disease, were infrequent and had rates lower than or comparable with those in most other countries.

  • Autoimmune thyroiditis was rare in the Marshall Islands.

  • There was a high prevalence of thyroid nodules (size > 4mm diameter), in the Marshall Islanders (in about 50% of women over 60 years old).

  • The frequency of thyroid nodules did not decrease with distance (a surrogate for dose) from Bikini, as had been suggested by Hamilton et al. (1987).

Conclusion The risk of thyroid nodules and thyroid cancer (papillary) on the islands of Rongelap and Utirik was increased but uncertainties in dose, and the fact that only 15% of the dose is believed to come from 131I, limits the quantitative inferences that can be drawn for numerical comparisons of risk with other 131I exposed groups. The evidence is strong for an increase in thyroid cancer and thyroid nodules in the high-dose Rongelap group. RECA compensation is not relevant since residents of these islands are already covered for compensation by separate legislation.

Semipalatinsk Test Site (STS) in Kazakhstan (former Russian Nuclear Test Site)

Persons who lived downwind of the nuclear testing at the Semipalatinsk Test Site (STS) in Kazakhstan (nuclear test period, 1949-1962) are being surveyed for

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

radiation-related thyroid disease. An initial small screening study was done in 1998 (1,990 subjects) and dosimetry has not been completed (Land et al., 2004).

Studies of Persons Exposed to Environmental Releases of Radioactivity from Nuclear Plants and Accidents

Chornobyl Studies

The largest increase in absolute thyroid cancer risk after the Chornobyl accident has been in children who were under 5 years old at the time of the accident, with a progressive decrease in observed risk to the age 18 years (Thomas et al., 1999). Ecologic studies have reported significant correlations between thyroid-cancer incidence and radiation exposure, but only two small published case-control studies (Astakhova et al., 1998; Davis et al., 2004a; Stepanenko et al., 2004) have shown higher estimated doses in the cases than in the controls. The Astakhova et al. study, in Belarus, found a strong trend for increased thyroid cancer with increasing dose (preliminary dose estimates). The Davis et al. study, in Russia, found a highly significant regression between thyroid cancer and dose (p < 0.009). The number of cases was small (26), and the doses imprecise, and some bias may have been due to unblinded interviewers about disease status; but the results were internally consistent and in agreement with other observations. Larger cohort and case-control studies include children in Ukraine and Belarus and are in progress based on measured thyroid doses. The method used to estimate individual thyroid doses in Belarus has been published (Gavrilin et al., 2004). Dosimetry methods and findings in Ukraine have been published (Likhtarov et al., 2005) with a forthcoming publication containing thyroid-cancer risk estimates from a cohort study in Ukraine (Tronko et al., Submitted). When published, those studies should provide well-grounded risk estimates of 131I that can be compared with those derived from external exposures (atomic-bomb survivors, Table 4.3; and medically treated subjects, Table 4.4).

The prevalence of noncancer thyroid disease in Chornobyl exposed children was surveyed among children in the Bryansk and Kaluga regions who were 10 years old or under at the time of the accident. Dose was estimated in about 2,500 of the children who were examined and had ultrasonography and thyroid-function biochemical tests. The diseases considered were thyroid nodules, cysts, and chronic thyroiditis. Diffuse goiter in young men (25 years old at the time of examination) was the only positive finding (the odds ratio [OR] at 1 Gy was 1.36 (95% CI = 1.05-1.99) (Ivanov et al., 2005). In contrast, a similar study of Nagasaki atomic-bomb survivors exposed to external radiation did not show a significant correlation with diffuse goiter but did have a significant dose-response relationship for nodule prevalence (Nagataki et al., 1994).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Hanford Releases: Hanford Thyroid Disease Study

The Hanford Thyroid Disease Study (HTDS) was mandated by Congress in 1988. The epidemiologic study was designed to examine whether rates of thyroid disease were higher than normal among people exposed to releases of radioactive iodine from the Hanford site during the period of highest releases, 1944-1957. The study was conducted by a team of investigators at the Fred Hutchinson Cancer Research Center. It covered 5,199 people identified from records of births during 1940-1946 to mothers whose place of residence was in one of seven higher-dose counties in Washington state. The study was a screening study consisting of a cohort selected on the basis of presumed past exposures to various levels of 131I released to the atmosphere from Hanford operations.

The major end points were thyroid cancer, benign thyroid nodules, hypothyroidism, and autoimmune thyroiditis. For each of those four categories, the study found that people with high doses had about the same amount of disease as people with low doses. There was no evidence of a statistically significant increase in any of the four diseases with increased radiation dose to the thyroid (Davis et al., 2004b). Problems associated with the dose correlations are inherent in environmental epidemiology studies and are discussed below.

Retrospective dosimetry: It is difficult to accurately estimate, and validate absorbed dose in environmental epidemiology studies in general and in each of the studies we have reviewed. The major uncertainties include the amount of radioactivity taken into the body and interindividual variation in metabolism and anatomy. An estimate of the average dose to people in a region is better defined than the dose to particular individuals. Validated person-specific dose estimates await the development of accurate tissue specific biomarkers. In addition, when different radiation sources are involved, other problems arise, as noted below.

Relative Biological Effectiveness: The effects from short-lived radionuclides of iodine, 131I, result from x and gamma rays known to differ in amount, but not in kind. The absorbed dose distribution differs significantly between alpha-, beta-, and gamma-emitting radionuclides, and short-range electrons emitted convey intense dose to nearby structures. The cancer risk coefficients for external x and gamma rays to the thyroid are based on better thyroid absorbed-dose estimates than those derived from internal-emitter studies, so the relative biological effectiveness of 131I vs x rays is still an open question; but current estimates place it at values near 1 for cancer induction from low LET radiation (UNSCEAR, 1993, and 2000). The dose from short-lived radionuclides of iodine from the Chornobyl accident is believed to be relatively minor (Gavrilin et al., 2004), but it is presumed to have had a substantial influence in the Marshall Islanders, in whom it constituted about 85% of the dose (Lessard et al., 1984; Lessard et al., 1985).


Conclusion The large increase in thyroid cancer observed in young children exposed to 131I intake from the Chornobyl accident is the first reliable evidence in

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

humans of an increased thyroid-cancer rate after relatively large exposure to 131I. It adds to the information derived from observations of the Marshall Islanders, who received even larger doses, mostly from radioactive isotopes of iodine other than 131I.

Studies of Thyroid Cancer after External Irradiation

The first data on radiation-induced thyroid cancer came from x-ray therapy of the head and neck in children. Followup of many medically irradiated populations has contributed much of the information on the magnitude of the risk, especially to children. Data on the risk to both children and adults also come from studies of the Japanese atomic-bomb survivors. Table 4.3 contains average ERR (AERR) at 1 Sv, and average excess absolute risk (AEAR) (104 PY per Sv) and summarizes the observed thyroid cancer risks estimated since 1990 in the major studies.

A 1994 incidence study of persons in the Life Span Study (LSS) includes 817,600 person-years of followup (Thompson et al., 1994). There were 132 observed cases of thyroid cancer, with higher risk coefficients in males than in females and a stepwise decrease with age in both.

The LSS cohort sample included 375,600 person years at risk for persons who were 0-19 years old at the time of the bomb (ATB). There were 59 thyroid-cancer deaths vs 22.2 expected, with a mean dose of 0.26 Sv. The AERR1Sv was 6.3 (95% CI = 5.1-10.1) and the AEAR was 3.8 (95% CI = 3.8 (2.7-5.4), values within the range of those observed in the incidence study; see Table 4.3.

The various medical studies summarized in Table 4.4 all found a significant increase in thyroid cancer after doses of 0.1-12.5 Sv. Variations in the risk coefficients may reflect differences in radiation sensitivity of children to different diseases for which radiation was administered and dosimetry uncertainties. Other

TABLE 4.3 Thyroid Cancer Incidence in the Japanese Atomic-Bomb Survivors. Average ERR, and Average EAR of Thyroid Cancer with Increasing Agea

Category

 

Observed

Expected

Mean Dose (Sv)

PY

AERR1Sv

AEAR 104 PYSv−1

Male

22

14.9

0.27

307,167

1.80

0.87

Female

110

79.4

0.26

510,388

1.49

2.32

ATBb 0-9

24

7.6

0.21

185,507

10.25

4.21

ATB 10-19

35

14.6

0.31

190,087

4.50

3.46

ATB 20-29

18

17.5

0.28

132,738

0.10

0.13

ATB > 30

55

54.5

0.25

309,224

0.04

0.06

ATB All

132

94.3

0.26

817,600

1.5 (0.5-2.1)

1.8 (0.8-2.5)

aModified from Table 17, UNSCEAR, 2000; page 408.

bAge at time of bomb.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

TABLE 4.4 Risk of Thyroid Cancer After External Radiation Exposure in Children

Study

Observed

Expected

Mean Dose (Sv)

PY

AERR1Sv

AEAR 104 PYSv−1

Shore et al., 1993

37

2.7

1.4

82,204

9.5 (6.9-12.7)

3.0 (2.2-4.0)

Tucker et al., 1991

23

0.4

12.5

50,609

4.5 (301-6.4)

0.4 (0.2-0.5)

Lundell et al., 1994

17

7.5

0.26

40,6395

4.9 (1.3-10.2)

0.9 (0.2-1.9)

Lindberg et al., 1995

15

8.0

0.12

37,0517

7.5 (0.4-18.1)

1.6 (0.09-3.9)

Ron et al., 1989

43

10.7

0.10

27,4180

34 (23-47)

13 (9.0-18)

Shore, 1990

13

5.4

0.24

34,700

5.9 (1.8-11.8)

9.1 (2.7-18.3)

Schneider et al., 1993

309

110.4

0.60

88,101

3.0 (2.6-3.5)

37.6 (32-43)

Ron et al., 1995

436

NA

NA

NA

12.0 (6.6-20)

3.5 (2.0-5.9)

possible explanations include differences in case ascertainment and in surgical removal of suspected thyroid neoplasms. The relative risk between 131I and external radiation is not well established. As in many of the other risk comparisons, the data on the atomic-bomb survivors provides the best information on risk as a function of age at exposure and dose. Ron et al. (1995) used a pooled analysis of data from seven cohort studies (atomic-bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for enlarged thymus), and two case-control studies of patients with cervical cancer and childhood cancer. The studies were conducted on almost 120,000 people about 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects) and included nearly 700 thyroid cancers and 3,000,000 person years of followup. For persons exposed to radiation before the age of 15 years, a linear dose-response relationship best described the data down to 0.10 Gy. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1-28.7) and the excess absolute risk per 104 PY per Gy (EAR/104 PY-Gy) was 4.4 (95% CI = 1.9-10.1). The ERR was greater (p = 0.07) for females than for males, but the findings from the individual studies were not consistent. The ERR began to decline about 30 years after exposure but was still increased at 40 years. Risk decreased significantly with increasing age at exposure; little risk was apparent after the age of 20 years. On the basis of the data, there was a suggestion that spreading dose over time (from a few days to over a year) may lower risk, possibly because of the opportunity for cellular repair mechanisms to operate. The thyroid gland in children has one of the highest risk coefficients of any organ, and there is convincing evidence of increased risk at 1.10 Gy (Ron et al., 1995).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

A high proportion of the thyroid cancers in the atomic-bomb survivors are accounted for by exposure at young ages. Little (2002) reports that over 50% of the excess cases associated with either the atomic bomb radiation or natural background radiation are linked to exposures under the age of 20 years, irrespective of the assumed risk model or natural background dose rate. The excess risk is overwhelmingly concentrated among females, again irrespective of the assumed model or natural background dose rate. Depending on the assumed natural background dose rate (in the range 0.5-2.0 mSv/year) between 17.3 and 32.0% of the thyroid cancers in this cohort may be associated with natural background radiation if an absolute-risk model applies; between 4.2 and 17.1% of the thyroid cancers may be associated with natural background radiation if the relative-risk model applies. The proportion of the thyroid tumors attributed to the atomic bomb radiation is between 21.1 and 22.0% for the absolute risk model, and is between 18.7 and 19.1% for the relative-risk model, in both cases irrespective of the assumed background radiation dose. The proportion of thyroid cancers accounted for by natural background radiation progressively increases with attained age, from 0.3% of cancers among those under the age of 15 years to 30.5% for those over the age of 60 years, assuming that the absolute-risk model applies. There is a similar increase in this percentage if it assumed that the relative-risk model applies (Little, 2002).


Conclusion The thyroid in children is highly sensitive to ionizing radiation from x rays and an increased incidence of thyroid cancer has been noted in some populations after doses as low as 0.1 Gy (Ron et al., 1995; Ron et al., 1989). The highest risk observed is in the youngest children, especially in females, and the increase in risk lasts for 40 years or more but at a decreasing rate in the later years.

Studies of Thyroid Cancer after Medical Administration of 131I

Two studies of children given 131I in diagnostic doses have reported small increases in the appearance of thyroid cancer. A Swedish study found 50 thyroid cancers when 39.4 were expected (SIR = 1.27, 95% CI = 0.94-1.71) after a mean dose of 0.5 Gy (range, 0-40.5) (Hall et al., 1996a). However, the study included a very small number of young children. No increase was noted when persons referred with the diagnosis of suspected tumors were excluded (Holm et al., 1988).

A study conducted, by the US Public Health Service, found five thyroid cancers when 2.53 were expected after a mean dose of 0.9 Gy (range = 0-20) (Hamilton et al., 1987). Three studies of mostly adults given 131I in therapeutic doses have been reported from Sweden, England, and the United States. The Swedish incidence study found 18 thyroid-cancer cases when 13.9 were expected (SIR = 1.29; 95% CI = 0.76-2.03) after doses over 100 Gy (Holm et al., 1991).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

The British study of cancer mortality after radioactive-iodine treatment of 7,417 thyrotoxic patients found decreased overall mortality (SIR= 0.83; 95% CI = 0.77-0.90) (634 observed/761 expected). Overall cancer mortality in the study was also decreased (SMR = 0.90, 95% CI = 0.82-0.98) (448 observed/499 expected). The thyroid cancer incidence, however was increased (SIR = 3.25, 95% CI = 1.69-6.25) (9 observed/2.8 expected) (Franklyn et al., 1999).

The US (NCI) mortality followup study found 24 thyroid cancer deaths when 6.09 were expected (OR=3.94, 95% CI = 2.52-5.86) after a mean dose of 50-70 Gy (Ron et al., 1998a). If one assumes a 5-year latent period and excludes deaths in the first 5 years after therapy, the OR falls to 2.6, which is of marginal statistical significance. Although doses to the thyroid could not be estimated adequately, no exposure-response was observed when administered activity was used as a proxy measure of dose.


Conclusions The thyroid cancer risk after medical 131I exposure is poorly documented, whereas the risk after exposure to external radiation is very well documented. The small number of children who received 131I in medical studies, and the medical considerations for the procedure, complicate interpretation of the findings, so there is little confidence in the results of the studies. The 131I risk coefficients derived from environmental-epidemiology studies are likely to be more reliable despite dosimetry uncertainties, which are being reduced by efforts to compute individual doses for Chornobyl and other populations exposed to 131I.

Thyroid Nodules after 131I Exposure

Thyroid nodules are common in the general population, and they increase in number with age (Tan and Gharib, 1997). Before the 1980s, most thyroid epidemiology studies report thyroid nodules on the basis of manual palpation; more recent studies report results based on thyroid ultrasonography. In both circumstances, the findings are buttressed by fine-needle aspiration or surgical biopsy, which provides the information needed to distinguish benign from malignant nodules. They are more prevalent in regions where the diet is low in iodine (Gembicki et al., 1997). When ultrasonography is used, the prevalence of nodules is about 60% in persons over 70 years old. Thyroid nodules are relatively rare in children under 18 years old (Mettler and Upton, 1995). The risk coefficients for thyroid nodules reported in heavily exposed (high-thyroid-dose) populations (Marshall Islanders) are up to 8 times higher than the risk coefficients for thyroid cancer.

A Food and Drug Administration-sponsored study of children who received diagnostic 131I (mean dose, 0.9 Gy) reported an ERR/Gy of 2.0 (95% CI = −0.5-12.5) for thyroid nodules (Hamilton et al., 1987). The frequency of thyroid nodules in 1,005 women given 131I for diagnostic function and imaging tests was compared with that in a comparison group of women (248) attending a mammog-

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

raphy screening clinic in a Swedish study (Hall et al., 1996b). The mean dose to the thyroid was 0.54 Gy, and the average age was 26 years old. The study found an ERR of 0.9 per Gy (95% CI = 0.2-1.9), but no difference in the ERR between those exposed under the age of 20 years, and those exposed after the age of 20 years.

External Radiations: Japanese Atomic-Bomb Survivors

The frequency of nodules was assessed with ultrasonographic screening in the Nagasaki Adult Health Study in 2,587 persons (61% women) 40 years old after exposure to the atomic bomb. The average dose was 0.77 Sv, and thyroid nodules were detected in 39 men and 151 women. A statistically significant increase in solid nodules was found only in women, but the authors did not describe the power of the test, nor did they calculate the ERR/Sv from their findings (Nagataki et al., 1994).


Conclusion Thyroid nodules increase in frequency with age, restricted intake of iodine in the diet, and radiation exposure. Only a small fraction of thyroid nodules become malignant. Given our review of the data and the fact that screening for thyroid nodules was considered and rejected by the Institute of Medicine for use in irradiated populations, we find no basis for reversing that recommendation. Thyroid nodules that progress and are diagnosed as malignant are covered under RECA.

STUDIES OF POPULATIONS OCCUPATIONALLY EXPOSED TO RADIATION

The causal association between exposure to ionizing radiation and the appearance of late effects, primarily cancer, was first recognized among groups of early radiation workers. Populations at risk for occupational exposure to radiation since the early 1940s have been subject to increasingly stringent occupational radiation-protection standards (Jones, 2004). Epidemiologic studies of such populations continue to make important contributions to the understanding of radiation-induced disease, particularly of the risks of late effects after low doses (< ~200 mGy [< ~20 rad]) that often are of public concern. The epidemiologic strengths and weaknesses of such studies must be borne in mind when reviewing their findings.

The strengths of the occupational population studies include the availability of large numbers of people, many of whom were individually monitored for radiation exposure on the job and have long periods of followup. In many instances, records exist of individual workers’ work and occupational-medicine histories and of the operations and processes. A weakness or limitation of the studies is that the worker populations have been predominantly healthy white

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

adult males 18-65 year old, often with regular access to health care, and do not include representative numbers of people who are unemployed because of illness or other factors and other segments of the general population, such as women, children, and other races—all factors that can influence health. Thus, results of many of the low-dose studies cannot be extended to other segments of the general population. Also, the characteristics of worker populations are recognized as contributing favorably to their mortality and illness experiences relative to the general population, a bias described as the healthy-worker effect (McMichael, 1975). However, that effect is generally considered to be greater for noncancer death or disease rates among workers when they are compared with segments of the general population of similar age, sex, and race than when those rates are compared with cancer rates, because it is difficult to screen from the workforce those who might develop cancer in the future. The average cumulative radiation doses to individual workers generally are low with the uncertainties that are inherent in monitoring data on individual workers, so total population dose tends to be both low and poorly estimated. Those limitations diminish the statistical power of the worker studies to evaluate the risk of radiation-induction of disease, primarily radiogenic cancers, at low doses. Other factors that can limit evaluation of the risks of disease at low doses are exposures to multiple agents, including one or more additional types of ionizing radiation from external and internal sources, and to chemicals and other workplace hazards and individuals’ lifestyle habits, often undocumented, such as smoking. Those factors limit the ability to detect and confirm a radiation-induced effect at low doses. Those issues have been discussed recently in more detail by Gilbert (2001) and Howe (2004).

In addition to uranium miners, millers, and ore transporters, several other groups of workers at risk of exposure to radiation have been followed over long periods to identify increases in causes of death relative to nonexposed comparison populations and to evaluate statistically significant relationships between such increases and occupational radiation exposures. The results have been increasingly available since the middle 1980s. They have particular relevance in considering the risks to the downwinders and onsite participant RECA populations because of the similarities between their radiation-exposure experiences and those of the occupationally exposed populations. Both these population groups were at risk of exposure to one or more types of radiation from external and internal sources at low doses and low dose rates over extended periods. They also probably had some similar non-occupational risk factors. Descriptions of most of the individual worker populations and findings published through the late 1990s are summarized in UN Scientific Committee on Effects of Atomic Radiation (UNSCEAR) reports (UNSCEAR 1994; 2000). For the purposes of this section, we discuss additional and updated epidemiologic studies of workers, other than uranium miners, millers, and ore transporters, who potentially were at risk of exposure to radiation on the job. The populations of interest are considered as five main but not always mutually exclusive groups; specifically:

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
  1. Nuclear-Industry workers;

  2. Commercial nuclear power-plant workers;

  3. Nuclear shipyard workers;

  4. Medical personnel; and

  5. Military participants at nuclear-weapons test sites and US nuclear submariners.

To address the committee’s charge regarding new epidemiologic information that might affect radiation risk estimates, the more recently reported findings of the major occupational epidemiologic studies, other than those involving uranium miners and millers, are summarized here.

Studies of Nuclear-Industry Workers

Epidemiologic studies involving nuclear-industry workers have been conducted or are in progress in several countries (UNSCEAR, 1994; 2000). Some of these studies have since been updated or have served as the basis of more focused studies of workers at the same or multiple sites and of specific cancers. Reports also are available of completed studies of workers at additional sites. They include studies of populations of civilians employed in the post-uranium-milling production and research and development operations of nuclear-energy and weapons-development programs at multiple facilities in the United States (US), United Kingdom (UK), Canada, the Russian Federation (formerly part of the Soviet Union), Japan, and France. In some of those countries, the operations began in the early 1940s.

Followup studies of mortality from all causes conducted during the 1970s and 1980s for a number of facility-specific populations of nuclear program workers in the US, the UK and Canada (NRC, 1990; UNSCEAR, 1994; UNSCEAR, 2000). The more robust of those studies established a basis for combined population studies in the individual countries (Gilbert and Marks, 1979; Smith and Douglas, 1986; Beral et al., 1985; Beral et al., 1988; Howe et al., 1987) and across all three countries (Cardis et al., 1995), external low LET radiation being the primary exposure of interest. Workers in nuclear industry operations in the UK, Canada, and Japan also are included in national registries of radiation workers.

Depending on the characteristics of their jobs, nuclear-industry workers were at risk for chronic exposure to low doses of various types of radiation primarily from external or internal sources, or both, and other potentially hazardous agents present in the workplace. Mortality from all and specific causes, including all types of cancers, generally is measured as the ratio of the number of deaths observed in the study population to a number expected in the comparison or “nonexposed” group (standardized mortality ratio [SMR]) and is the main result reported in most of the studies. In many of those and other previously reported studies of nuclear-industry workers, the SMRs for total mortality and noncancer

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

system-specific diseases are less than unity, reflecting a healthy-worker effect. Cancer mortality typically is similar to that expected among the general population, although some statistically significant increases in various site- or type-specific cancer mortality are noted. However, with the exception of nonCLL leukemia, there is a lack of evidence of a consistent pattern of such increases (Telle-Lamberton et al., 2004) or of their attribution to occupational radiation exposure. A causal association between chronic exposure to low doses of low LET radiation and multiple myeloma remains equivocal. In some studies, nonexposed workers or workers in different dose or job groups at the same facility are used as internal controls when radiation dose-response relationships are examined for all or site-specific solid cancers and leukemia, thereby taking the healthy-worker effect into account. The major, more robust studies have provided risk estimates expressed as excess relative or absolute risks (ERR, EAR, respectively) for radiation induction of radiogenic cancers and nonCLL leukemia respectively. To date, only a few morbidity studies of nuclear-industry workers have been conducted. Those have tended to focus on subcohorts of workers at nuclear facilities, who also were at risk of exposure to specific radionuclides, such as plutonium or nonradioactive toxic metals or chemicals.

Some previously evaluated facility-specific studies of nuclear workers have since been updated or have served as the basis of more focused studies of workers at the same or multiple facilities and of workers with specific exposures or cancers. Reports on recent studies of workers at additional nuclear sites also are available in the peer-reviewed literature. In Table 4.5, we reference the major studies in those categories and summarize their significant findings with respect to a risk for radiation-induced cancers and nonCLL leukemia as available.

Studies of Commercial Nuclear Power-Plant Workers

Workers at commercial nuclear power plants (CNPPs) are primarily at risk of chronic exposure to low external doses of high-energy penetrating radiation (x and gamma), and to a lesser extent to neutrons externally and possibly of alpha-particle emitters (such as, uranium, radium, and radon) and low energy beta emitters (such as, tritium, 3H) internally. The findings of two large combined-population cohort mortality studies have recently been reported; both focused a priori on evaluation of relationships between radiation and the risk of solid cancers and leukemia (except CLL).

Zablotska et al. (2004) followed a cohort of 37,735 male and 7,733 female employed and monitored for at least 1 year at four Canadian nuclear power plants in 1957-1994 with a total of almost 608,000 person year at risk (individual mean = 13.4 year). Cumulative radiation exposures (equivalent doses) for individual workers ranged from 0 (31.6%) to 498.9 mSv (49.9 rem) (mean = 13.5 mSv [1.25 rem]). Compared with the Canadian general population, mortality in male and female workers combined from all causes (1,599 deaths; SMR = 0.63, 95%

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

TABLE 4.5 Risk Estimates for Mortality from Selected Cancer Groups Among Atomic-Bomb Survivors and Cohorts of Nuclear-Industry Workers (Not Including Uranium Miner or Millers)

Study

Cohort Sizea

Mean dose (mSv)

No. of deaths, All Causes/All Cancers

ERR:All Cancers Except Leukemia

ERR: Leukemia Except CLL

Significant Specific Cancer Increasesb Other Than Leukemia

ERR/Sv

CI

ERR/Sv

CI

Atomic-bomb survivors (Pierce et al., 1996)

86,572

NA

NA/7,578

0.24c

0.12,0.4

2.2c,d

0.4,4.7

NA/NA

IARCe (Cardis et al., 1995)

95,673

40.2

15,825/3,976

−0.4,0.3

−0.07

2.2

0.13,5.7

Multiple myeloma, 44 deaths p = 0.037 (1-sided)

NDRCf (Ashmore et al., 1998)

206,620

6.3

5,426/1,632

3.0g

1.1,4.9

0.4

−4.9,5.7

0 (CI 90%)

NRRWh (Muirhead et al., 1999)

124,743

30.5

NA/3,596

0.09

−0.3,0.5

2.6

−0.03,7.2

0 (CI 90%)

JNIWRi (Iwasaki et al., 2003)

175,939

12.0

2,934/1,191

NA

NA

0.01

−10.0,10.0

0 (CI 95%)

SETCEAj (Telle-Lamberton et al., 2004)

58,320

NA

4,809/1,898

NA

NA

NA

NA

Pleural cancer, 28 deaths, SMR = 1.79 Melanoma, 24, SMR = 1.50

aTotal number of men and women.

bConfidence intervals.

cAdjusted for the effects of time since exposure and for nonlinearity in dose.

dBased on male atomic-bomb survivors ages between 20 and 60 years at exposure. as presented by Murihead et al., 1999.

eInternational Agency for Research on Cancer.

fNational Dose Registry of Canada.

gEstimate for men, estimate for all cancers in women = 1.5/Sv, (90% CI = −3.3. 6.3).

hNational Registry of Radiation Workers, UK.

iJapanese Nuclear Workers Registry.

jSuivi Epidemilogique des Travaillersdu Commissariat a l’Engergie Atomique, France.

NA = Not available.

SOURCE: adopted from Gilbert, 2001.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

CI = 0.60-0.66) and all cancers (531 deaths; SMR = 0.74, 95% CI = 0.68-0.80) demonstrated a “healthy-worker” effect typical of a relatively young workforce. Deaths due to leukemia except CLL, for males and females combined, were fewer than expected, but the deficit was not statistically significant (18 deaths; SMR = 0.80; 95% CI = 0.47-1.26). The RRs for nonCLL leukemia increased monotonically across the four dose groups (<1, 1-49, 50-99, and >100 mSv) on the basis of one death in each of the two highest dose groups. ERR/Sv for all solid cancers (2.80, 95% CI = −0.038-7.13), and nonCLL leukemia (52.5, 95% CI = 0.205-291) were higher than those for the atomic-bomb survivors (Little and Muirhead, 1998) and the International Association for Research on Cancer (IARC) combined analysis of nuclear workers (Cardis et al., 1995), but the authors considered that they could have been due to chance. Uncertainties associated with the relatively small numbers of deaths to date also could have contributed to the findings.

A companion study (Howe et al., 2004) of US CNPP workers evaluated noncancer and cancer mortality among a predominantly male cohort (N = 53,698) with individual radiation monitoring data for at least a year while they were employed at 52 facilities nationwide some time between 1979 and 1997. As in the study by Zablotska et al. (2004), a marked healthy-worker effect was seen for noncancer deaths (773 deaths; SMR = 0.34, 95% CI= 0.32-0.36) and all solid-cancers deaths (368 deaths; SMR = 0.65, 95% CI = 0.59-0.72) relative to the general US population. However, positive but not statistically significant associations with radiation dose were seen for nonCLL leukemia (26 deaths; ERR/Sv = 5.67, 95% CI = −2.56-30.41) and for all solid cancers (368 deaths; ERR/Sv = 0.506, 95% CI = −2.01 - 4.64). The finding of a high mortality risk, ERR/Sv 8.78 (90% CI = 2.19-20.0) from arteriosclerotic heart disease in the worker population is considerably higher than reported in the LSS where the authors also found a significantly increased heart disease mortality risk (ERR/Sv = 0.17, 90% CI = 0.08-0.26) p = 0.001 (Preston et al., 2003). In contrast, the incidence of heart disease in the adult health study for about 10,000 participants during the period 1958-1998 (Yamada et al., 2004) showed no significant relationship with radiation dose for any of the cardiovascular diseases. The high rate of heart disease observed by Howe et al. (2004) was noted as being out of line with other observations, and they advised that further attention to the issue was warranted. McGale and Darby (2005) systematically reviewed the published findings of studies of mortality (25 studies) and morbidity (one study) from circulatory disease among various populations, including some worker populations at risk for exposure to radiation doses between 0-5 Sv. The authors concluded that there is no clear epidemiologic evidence of a risk of circulatory diseases at 0-4 Sv, as was suggested by the study of atomic-bomb survivors (Preston et al., 2003).

Because the commercial nuclear-power industry was established somewhat later than the nuclear-energy and weapons-development programs, mortality and the years of followup available for CNPP workers are less than for workers in the nuclear-development programs, so the statistical power of these studies is more

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

limited. However, CNPPs provide the opportunity for followup studies of large cohorts of individually monitored people at risk of exposure to radiation at occupationally low levels, and both cohorts are included in the combined analysis of mortality among nuclear workers in 15 countries that is being coordinated by IARC.

As illustrated by the summary reviews, there are benefits to being able to evaluate the human risks posed by exposure to low levels of radiation through direct observation and measurement of exposed populations. They allow evaluation of the cancer risks estimated with extrapolation from data on populations such as the atomic-bomb survivors, who were exposed at high dose rates over a much wider range of doses—from very low doses to several Gy—than those measured directly in the low-dose and low-dose-rate populations. Such comparisons can show whether the cancer risk estimates obtained by extrapolation for low exposure levels significantly underestimate or overestimate the risks obtained through direct measurement. Also, despite their limitations, the multiple low-level exposure studies contribute to the “weight of evidence” with respect to the validity of the cancer risk estimates obtained by extrapolation that contribute to the basis of current radiation-protection standards.

Studies of Nuclear Shipyard Workers

Between the early 1950s and 1970s civilians were employed in the US naval nuclear propulsion program at facilities nationwide where they were involved in building and overhaul of US nuclear naval vessels. In those activities, workers were at risk of external exposure to gamma radiation from cobalt-60 and other radionuclides deposited in the nuclear reactor systems and to asbestos and industrial chemicals.

A recent study by Silver et al. (2004) has updated through 1996 the mortality experience with respect to radiation status of an expanded cohort of 37,853 predominantly white civilian men and women employed at the Portsmouth Naval Shipyard (PNS), Kittery, Maine, some time between 1952 and 1992. This population originally was the subject of a proportional mortality analysis that found greater than expected proportions of leukemia and all cancers among the men (Najarian and Colton, 1978). Reports of those findings, attributed to methodologic shortcomings, contributed to the concerns raised in 1978 that led to the formulation and eventual enactment of RECA 1990 as described in Chapter 2.

More rigorous followup studies of mortality from all causes (Rinsky et al., 1981), leukemia (Stern et al., 1986), and lung cancer (Rinsky et al., 1988) in a cohort of almost 25,000 white civilian men employed at PNS some time between 1952 and 1977 found leukemia and all-cancer mortality within the range expected among a comparable component of the US population, an increased risk of lung cancer in workers with career doses of at least 1 rem (10 mSv) externally and at least 15 years after first exposure and an increased risk of nonCLL leuke-

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

mia in workers in the same group exposed to at least 1 rem (10 mSv)—with no latent interval period. However, the increased lung-cancer risk with respect to radiation appeared to be smaller when exposures to asbestos and welding fumes were taken into account, and no statistically significant association was found between leukemia and radiation or solvent exposure, although there was an increased risk of leukemia in electricians and welders.

PNS employees also were included in a combined population study of mortality that involved almost 62,000 civilian workers at eight US naval shipyards that serviced nuclear powered vessels (Matanoski, 1991). This study was designed to determine whether there was an excess risk of leukemia or other cancers in the population that was associated with their occupational radiation exposure to low doses of gamma radiation. Three subcohorts were identified for comparison; they were: nonradiation workers; radiation workers with individual cumulative external doses of 0.5 rem (5 mSv) or less; and radiation workers with more than 0.5 rem (5 mSv). The overall mortality risks in all three groups were generally similar to those in the US general population but were highest for the nonradiation-worker group and significantly lower than expected for the > 0.5 rem subcohort. The risks of nonCLL leukemia and lymphoma in the radiation worker groups were lower than those for the general population and the nonradiation workers. However, the risk for the > 5 rem group was greater than that for the < 0.5 rem group. The lung cancer risk was higher in the nonradiation worker group relative to the general population and slightly, but not significantly higher in both groups of radiation workers. However, this increased risk appeared to be associated with the effects of workers’ exposure to asbestos rather than to radiation.

In the updated study of the PNS cohort (Silver et al., 2004), the healthy-worker effect was less evident than previously observed by Rinsky et al. (1981); overall mortality in the full cohort was similar to that expected for the US population (12,393 deaths; SMR = 0.95, 95% CI = 0.93-0.96). Mortality from all cancers (3,192 death; SMR = 1.06, 95% CI = 1.02-1. 10) was statistically greater than expected, owing in large part to increased risks that were statistically significant for cancers of the trachea, bronchus, and lung in exposed radiation workers (monitored with > 0.0 mSv) and workers who were not monitored for radiation; confounding was associated with asbestos exposure in the radiation workers and smoking in the nonmonitored workers. Leukemia mortality in the full cohort, although slightly increased was similar to that in the general population (115 deaths; SMR = 1.01, 95% CI = 0.84-1.22) but was lower among the exposed and unexposed monitored subcohorts, whereas it was nonstatistically increased among the nonmonitored subcohort. However, a positive dose-response relationship was observed between leukemia and cumulative external radiation dose; the authors interpreted this as being consistent with the conclusions of other reviews of leukemia among nuclear workers (Schubauer-Berigan and Wenzl, 2001).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

Studies of Medical Personnel

Radiologists and Radiotherapists

Since the discovery of x rays by Roentgen in 1896, many physicians, technologists and physicists have been occupationally exposed to radiation at dose levels that changed substantially over time. Before 1920, when the British Radiological Society was formed and procedural standards were formulated, high doses were received by practitioners. Therapists who used manually inserted radium needles received very high doses to the fingers, and many lost digits from overexposure. Diagnostic radiologists did not wear protective shields, and they received much higher doses than was the norm in later years. The doses to those radiation workers were fractionated, delivered over many years, and very high by current standards. The turning point with respect to the protection of radiation workers in the United States was a 1928 international meeting that led to the adoption of the roentgen as the radiation unit and the creation of the group that led to the formation of ICRP and the introduction of occupational radiation-protection standards in the United States.

All followup studies on radiologists are hampered by lack of individual dose data. During the 1920s and 1930s, doses to individual radiologists were estimated to be 1 Sv per year (Braestrup, 1957). Smith and Doll (1981) estimated annual doses to British radiologists at 0.1 Sv before the 1950s and perhaps 0.05 Sv in the early 1950s, and they declined to 0.5 mSv by 1993 (Hughes and O’Riordan, 1993). The total number of 8 cases of leukemia were observed among British radiologists who had registered with a radiological society after 1920. The fact that radiation pioneers received doses likely to have been higher than the pre-1950 annual average (0.1 Sv) is a potential source of bias.

A report on mortality among almost 2,700 British radiologists who practiced in 1897-1997 reveals a number of important findings regarding the particular tumors that were increased and the periods involved (Berrington et al., 2001). Although the number of cancer deaths among radiologists registered after 1920 was similar to that expected among all medical practitioners, there was a statistically significant trend (p = 0.002) toward increasing cancer mortality with time since entry into practice (registration with the British Radiological Society), so that those registered for more than 40 years after 1920 had a 41% excess risk of cancer mortality (SMR = 1.41, 95% CI = 1.03-1.90). Practitioners who entered practice after 1954 did not show increased mortality from cancer, so the trend was most likely due to the highest mortality risk in the earliest period. In those registered after 1920 when the first recommendations for radiological protection were published in Britain, the death rates from cancer in radiologists were not greater than the death rates in all other medical practitioners combined (SMR = 1.04, 95% CI = 0.89-1.21). No evidence was found of increased mortality other than from cancer even in the earliest radiologists despite the fact that the esti-

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

mated dose they received has been associated with more than a twofold increase in death rate in the Japanese atomic-bomb survivors. The greatest proportional excess in the post-1920 radiologists was in leukemia. Mortality from noncancer causes was lower than in the comparison populations even in the pre-1921 radiologists, who would have received the highest doses. The latter finding is at odds with recent noncancer-mortality data on the Japanese atomic-bomb survivors.

Parallel studies of radiologists carried out in the United States reached many of the same conclusions (Seltser and Sartwell, 1965; Matanoski et al., 1975a, b, 1984 cited in Yoshinaga et al., 2004). The turning point in the United States was a 1928 international meeting that led to the adoption of the roentgen as the radiation unit and the creation of the group that led to the formation of ICRP. The SMRs for US radiologists compared with other specialists were 1.38 for all cancers and 2.01 and 1.0 for leukemia for those who entered the specialty during the periods 1920-1939, and 1940-1969 respectively. SMRs for leukemia in the UK radiologists were 2.5, 2.7, 2.29, and 1.16 for those who registered with the British Radiological Society in the periods 1897-1920, 1921-1935, 1936-1954, and 1955-1979, respectively. For all cancers, the UK radiologist’ SMRs were 1.58, 1.04, 0.91, and 0.78 for the same period. Thus, similar trends in leukemia and all-cancer mortality were observed in both groups.

Matanoski et al. (1984) noted a nonstatistically significant relative risk (RR = 2.1) for multiple myeloma in the US radiologists who joined the Radiological Society of North America in 1940-1969 when compared with other physician specialty groups. No increase was seen among the earlier member cohort (1920-1939). Berrington et al. (2001) also noted a similar increase in the risk for multiple myeloma (2.32) on the basis of four deaths among the later UK radiologists (> 1940-1969) but not for the earlier cohort (>1920-1939). Several hypotheses have been offered for the finding that the risks for nonCLL leukemia for the later cohort at entry appear to decrease while the risk for multiple myeloma increased but to date it remains unexplained (Matanoski et al., 1984).

Radiological Technologists

There are many more radiologic technologists than radiologists, and they spend more hours in conducting procedures. It is estimated that there are 2.3 million medical-radiation workers worldwide. About 146,000 radiologic technologists were followed for mortality through 1990 (Doody et al., 1998, Mohan et al., 2003). The cohort included all technologists living in the US who were certified for at least 2 years between 1926 and 1982. The cohort was composed primarily of women, in contrast with the radiologist cohorts analyzed that were limited to men. A smaller cohort consisted of 6,500 male x-ray technologists trained by the army during World War II. They were followed through 1963 (Miller and Jablon, 1970) and 1974 (Jablon and Miller, 1978) with death certificates obtained through Veterans Administration files (See Tables 4.6 and 4.7).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

TABLE 4.6 Mortality Risks Observed in Radiology Technologist Studies

Technologists

Sex

SMR/Number of Deaths Observed in Study Population

All causes

All cancer

Leukemia

US 1926-1982 Mohan et al., 2003

Female

0.76/7567

0.86/2558

0.92a/98c

US 1926-1982 Mohan et al., 2003

Male

0.76/5057

0.73/1137

0.95a/60c

US Army, 1946-1963 Jablon and Miller, 1978

Male

1.06/289

1.05/55

1.25b/8

aComparison vs US population.

bComparison vs pharmacy and lab technologists.

cNot including CLL.

Higher leukemia SMRs were found in Japanese male x-ray technologists (Mohan et al., 2003), and higher leukemia SIRs were found in Chinese male and female x-ray workers than in US radiation technologists (Sigurdson et al., 2003). The higher rates are presumed to reflect higher exposures. The SMRs and SIRs observed in radiologists and technologists working in the US, UK, Japan, China, and Denmark have been summarized by Yoshinaga et al. (2004). As was found for the radiologists studied, the most consistent observation was an increased leukemia risk in the early cohorts of medical-radiation workers. The lack of individual dose estimates in the years before personal dosimetry was in wide use compromises the ability to capture dose-response information from the historical studies. Future data should not be so limited, albeit with lower individual exposure doses.

TABLE 4.7 Standardized Incidence Ratios/Number of Persons Observed in US Radiation Technologist Studies

Technologists

Sex

SIR/Number of Cases Observed in Study Population

All causes

All cancer

Leukemiaa

US 1926-1982 Sigurdson et al., 2003

Female

NA

1.07/2408

1.12/48

US 1926-1982 Sigurdson et al., 2003

Male

NA

0.94/884

1.04b/27

aAll types of leukemia including CLL.

bComparison vs US SEER Program.

NA = Not applicable.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

Military Participants at Nuclear-Weapons Test Sites

More than 200,000 US military personnel participated in atmospheric nuclear-weapons tests between 1945 to 1963. In the late 1970s concern about the long-term health of the participants in those tests, particularly the risk of leukemia and other cancers, prompted a series of followup studies, primarily of mortality among groups of military personnel identified as having participated onsite at the ‘SMOKY’ (1957) or at least one of five other test series conducted at the Nevada (NTS) or Pacific (PTS) Test Sites between 1953 and 1956 (Caldwell et al., 1980; Caldwell et al., 1983; MFU, 1985). Those studies found no consistent disease patterns. Compared to the US population, leukemia incidence and mortality was significantly increased among the more than 3,000 SMOKY participants, based on small numbers of leukemia deaths, but not in some of the other groups. Average individual and the total population radiation doses accumulated during the test periods were generally low, although a few participants received > 50 mSv (5 rem) during the test year; dose-response relationships were not evaluated.

Subsequent studies by Watanabe et al. (1995b) and Johnson et al. (1996) updated and evaluated mortality among 8,554 and approximately 40,000 US Navy veterans who participated in HARDTACK I (PTS 1958) and CROSSROADS (Bikini 1946) tests, respectively. Followup for the HARDTACK 1 cohort was from September 1, 1958 through September 1, 1991; it was through December 1992 for the five series test study. Veterans who had not participated in the tests comprised the comparison groups for these studies. The median dose of gamma radiation was 3.88 mSv (388 mrem) among the HARDTACK I veterans. Comparing unadjusted mortality ratios for the HARDACK 1 veterans and their comparison group, Watanabe et al. (1995b) found a statistically significant increase in deaths from all causes (1,083 deaths, RR = 1.10, 95% CI = 1.02, 1.19), but a nonsignificant deficit in leukemia deaths (6 deaths; RR = 0.69, 95% CI = 0.27-1.78). Mortality from other cancer causes, except for cancers of the digestive organs, was similar in both groups; only digestive organ cancer mortality was statistically significantly increased (66 deaths, RR = 1.47, 95% CI = 1.06 -2.04). The dosimetry data available for the CROSSROADS study were considered unsuitable for epidemiologic analyses, so mortality was compared for three surrogate exposure groups: veterans who boarded target ships and thought to be at highest risk of exposure; those who did not, and a special tasks group. In that study all causes mortality among participants was slightly increased (~5%) compared with the nonparticipant veteran group. Small increases seen in mortality from all cancers (1.4%) and leukemia (2.0%) were not statistically significant. Thus, results of those studies were equivocal with respect to a radiation effect.

Subsequently, a mortality study was designed to update the five test series study and to analyze the timing and causes of death of about 70,000 servicemen who participated in at least one of five selected nuclear-weapons test series in the

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

1950s; almost 65,000 comparable nonparticipants served as the comparison group. More than 5 million person/year of mortality followup information was obtained. Overall, the participants and the comparison group had similar risks of death and cancer except that the participants had a 14% higher risk of leukemia than the comparison group. That higher risk was not statistically significant and was possibly real but also could have been a chance finding (IOM, 2000).

A study was conducted of 1,010 US veterans who had received the highest gamma-radiation doses (50 mSv [5 rem] or more per year) during the 1958 HARDTACK I test series. Cancer rates were compared with those in a group of 2,870 participants in lower-dose tests. Mortality from all causes (RR = 1.22, CI = 1.04-1.44) and from all lymphopoietic cancers (RR = 3.72, CI = 1.28-10.83) was significantly higher in the high-dose cohort than in the low-dose controls (Dalager et al., 2000).

Mortality and incidence of cancer in participants in the United Kingdom’s (UK) weapons tests held during the 1950s and 1960s at bases on islands in the Pacific Ocean and in Australia, was updated through 1991 for 21,358 service personnel and civilians and a control group of 22,333 nonparticipants (Darby et al., 1993a), most of whom were included in an earlier followup study (Darby et al., 1988). During the seven years of further followup, the number of deaths in the test participants were fewer than expected from national rates. SMRs for all causes were 0.86, all neoplasms 0.85, leukemia 0.57, and multiple myeloma 0.46. In the period more than 10 years after initial participation, relative risk in the participants was near unity for all causes (0.99 CI = 0.95-1.04) and all neoplasms (0.95 CI = 0.87-1.04). Leukemia mortality was equal to that expected from national rates but greater than in controls for both the followup period (1.75 CI = 1.01-3.06) and the period 2-25 years after the tests (3.38 CI = 1.45-8.25). The authors concluded that participation in nuclear weapons tests had no detectable effect on life expectancy or on the development of cancer. They attributed the apparent increase in leukemia in participants to an apparent deficit in rates observed in the controls, although a small risk of leukemia could not be excluded.

Mortality and cancer incidence between 1957 and 1987 were evaluated among a small cohort of New Zealand naval personnel (n = 528) who participated in UK nuclear weapons tests in 1957 and 1958 at Pacific island bases and 1504 nonparticipant naval controls (Pearce, 1996; Pearce et al. 1997). Mortality from all causes combined, all causes other than cancers and all cancers combined, though increased in the participants relative to the nonparticipants in some cases, was as expected. The RRs for cancer incidence overall (RR = 1.12, 90% CI = 0.78-1.60); and the incidence of cancers other than hematological malignancies (RR = 1.14, 90% CI = 0.69-1.83) were slightly but not statistically significantly increased. Hematological cancers accounted for seven deaths among the participants (RR = 3.25, 90% CI = 1.12.-9.64) including four from leukemia (RR = 5.58, 90% CI = 1.04-41.6), one of which was the CLL type (Pearce et al., 1997). No cases of multiple myeloma were identified among the participants. The small

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

numbers of leukemia and the wide confidence intervals do not provide strong evidence of a radiation effect although it cannot be ruled out.

The committee comes to the same conclusion as the authors of the different reports concerning the mortality experience of military participants at nuclear test sites: the lack of a consistent pattern of cancer excess, with the only statistically significant increased mortality for lymphopoietic cancers suggests that factors other than or in addition to radiation may have been involved.

Study of US Nuclear Submariners

Mortality rates for all-cause and specific-disease categories in a cohort of 76,160 men who served in US nuclear submarines between January 1, 1969 and June 30, 1982 were compared with those in the comparable segment of the US population (Charpentier et al., 1993). During the study period the cohort accumulated almost 595,800 person/year and about 32,000 person/rem (mean cumulative dose to individuals 1.70 mSv [.0.17 mrem]). Notably, a statistically significant deficit of mortality was seen for all causes of death (811 deaths, SMR = 0.62, 95% CI = 0.58-0.66) combined and all cancers (77deaths; SMR = 0.71, 95% CI = 0.56-0.88) combined. However, as the authors noted, the study findings should be interpreted cautiously, because in addition to a marked healthy-worker effect, the cohort was relatively young (mortality through the study period of just over 10%) and the periods of radiation exposure and followup were relatively short. The authors evaluated mortality with respect to several measures including radiation dose, but did not develop cancer risk estimates.


Conclusion Except for leukemia in some but not in all studies reviewed, the epidemiologic studies of populations occupationally at risk from chronic exposure to low doses of ionizing radiation continue to show a lack of a consistent pattern of statistically-significant mortality excesses related to radiation dose for the radiogenic cancers that currently are compensable under RECA (Table 2.1). A causal association between chronic exposure to low doses of low LET radiation and multiple myeloma remains equivocal. Apparent excess mortality from other specific cancers identified among the various worker populations were described by the study authors as chance findings, or were attributed to small numbers of deaths, or to factors other than radiation, including exposure to other workplace hazards. To date, studies of these populations also fail to show any evidence of increased mortality risks related to dose for cancers identified in Table 3.6 that are not compensated under RECA.


Conclusions The committee reviewed information about the long-term risks to human health posed by radiation exposure that has been published since the BEIR III report in 1980, which was the basis of the original RECA legislation in 1990. Our review focused on epidemiologic studies that we considered pertinent to the RECA

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

populations with respect to the types of radiation to which they were potentially exposed, the duration and magnitude of their exposure, and the cancers and other diseases that are compensable under RECA. We included data on all the cancers for which a radiation risk increase has been documented. In some of the less common cancers, such as cancers of the salivary gland and the small intestine, the data were too sparse and no numerical risk estimates were found in our review of the literature.

We found no evidence that the results of epidemiologic studies of radiation-exposed populations reported since RECA was formulated, substantially change the current estimates of risk of radiation-induced diseases among the RECA populations.

We concluded that to date the risk estimates for radiation-induced cancers and nonCLL leukemia obtained from the more statistically-powerful occupational studies for exposure to chronic low doses generally are consistent with those estimated for the low dose range obtained by extrapolation from the atomic-bomb survivors’ data.

While recognizing the limitations of the epidemiologic studies of populations occupationally at risk of chronic exposure to low doses of low LET radiation, our review of the studies of such populations has provided little evidence of increased risks for disease related to low radiation doses, particularly for most of the site- or type-specific cancers compensable under RECA. These findings suggest that it is unlikely that onsite participants and the downwinders, particularly those who may have been exposed as adults to fallout from US nuclear weapons operations, are at significantly increased risk for cancers that are currently compensable under RECA, except possibly for nonCLL.

RECENT DEVELOPMENTS IN RADIATION BIOLOGY

This section discusses recent findings in radiation biology that might have a direct or indirect effect on cancer risk coefficients. Such information might result in a reconsideration of populations and geographic regions that RECA covers.

The dose-response relationship for the induction of tumors by ionizing radiation is generally described as being a LNT response. The risk assessment for cancer is based on human tumor data and so, relies directly neither on the use of cellular- and molecular-biology data, nor on the frequencies of radiation-induced tumors and genetic effects in laboratory animals. However, such data are used as part of the evidence for the LNT hypothesis. Thus, the committee does consider factors that might influence the shape of tumor dose-response the effects of genetic variation. Those may become important if, as has been discussed by UNSCEAR (2001), for example, future dose-response approaches to risk assessment are more biologically based than is currently the case.

Cellular and molecular radiation-biology studies have been used extensively to provide support to the LNT approach for extrapolation of tumor responses

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

from low or medium doses to those at very low doses (NCRP, 2001). Gene mutations and chromosomal alterations have been shown to be involved in the formation of tumors, including radiation-induced ones (reviewed in Meltzer et al., 2002 and NCRP, 2001). Many studies have demonstrated that gene mutations and chromosomal alterations increase with radiation dose and that they are induced in a LNT manner at low doses (under 5 mGy). However, in recent years, several radiation-induced processes have been described by which radiation might either increase or reduce the frequency of those genetic alterations at very low doses compared with the currently accepted LNT extrapolation from low or medium doses. No effect of those cellular processes on cancer risk has been established at this time (Morgan, 2003).

Bystander Effects

The bystander effect is described as a response in cells that are not directly traversed by a radiation-particle track. The majority of such responses have been described for high-LET exposures (such as to alpha particles) because it is possible, using a microbeam or specific dose, to define the cells traversed or the proportion of the cell population irradiated. For low LET radiation (such as x-rays and gamma rays), unless specific energy microbeams are used, all cells are traversed by multiple ionization tracks. Thus, no measurable bystander effect will occur.

The bystander effect has been observed in several experimental in vitro systems and a variety of mechanisms have been proposed to explain it (Mothersill and Seymour, 2001). The lack of consensus illustrates the degree of speculation that is involved in the interpretation of bystander experiments, and this in turn results in an inability to relate the phenomenon directly to risk. Whether a bystander effect can be induced after in vivo irradiation is still quite uncertain. Thus, a concern remains as to just how relevant the in vitro cellular results are for predicting in vivo responses and how pertinent they are to the process of tumor induction. Certainly, the organization of tissues, as compared to cell cultures, and the nature of cell-cell interactions in vivo vs those in vitro support an overall concern about the relevance of the in vitro studies.

Two recent studies support the view that the use of in vitro approaches does not necessarily predict in vivo outcomes. Weaver et al. (2002) showed in an elegant set of studies that tumor cells in a three-dimensional organization responded to apoptotic (programmed cell-death) signals differently from the same cells grown on flat tissue-culture substrates. The data show that analyzing cell interactions in a more natural three-dimensional setting provides a view that is closer to what happens in living organisms. Prise et al. (2002) lend support to that view. They showed that multicellular, tissue-based models provide evidence of competing bystander processes at low doses of high-LET radiation, both protective and adverse ones. Those outcomes are quite different from the responses described for in vitro cellular systems.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

Genomic Instability

The development of widespread genomic instability is a hallmark of tumor development. Such instability is both a cause and a consequence of the cancer process. The type of genomic instability described after radiation exposure is different from and much more limited than that observed in tumors (Little, 1998). Most studies that have investigated genomic instability have involved irradiating cells in vitro and observing the appearance of de novo genetic changes in descendants of irradiated cells. A few studies have shown increased genetic damage in descendants of irradiated cells that have been transplanted into whole animals, but there is no substantial evidence of the effects being induced and transmitted in vivo.

Adaptive Response

An adaptive response to radiation exposure has been described for chromosomal alterations and mutations for both in vitro and in vivo exposure (UNSCEAR, 1994). The phenomenon is one whereby the frequency of chromosomal aberrations was found to be approximately 50% lower after a small priming dose (such as 10 mGy) followed by a challenge dose of 1 Gy or more compared to the frequency after a challenge dose of 1Gy or more without a priming dose.

A number of possible explanations of the adaptive-response phenomenon have been proffered, but none has convincingly explained it. In addition, the adaptive response is highly variable and depends on the cellular (or tissue) system used. For human cell studies, samples from some people show an adaptive response, and those from others do not. The induction of an adaptive response appears to be transitory, that is, the protective effect of the priming dose generally lasts for only a few hours. Furthermore, very small doses and dose rates, of the kind encountered environmentally, do not seem to induce an adaptive response. Having reviewed the literature on the induction of an adaptive response, National Council on Radiation Protection and Measurements (NCRP) Report 136 (NCRP, 2001) concluded that the data are generally interpreted not to exclude the LNT model and thus do not provide sufficient grounds for rejecting the LNT dose-response model as a basis for assessing the risks posed by low-level ionizing radiation in radiation protection.

Genetic Susceptibility

The evidence is clear that certain genotypes enhance susceptibility to cancer of different types. A subset of those genotypes can confer sensitivity to radiation-induced cancer. At the population level, these mutations are predicted to have little overall effect on cancer risk estimates, because their frequency in the population is very low (around 1 per 10,000 live births). That view is supported by computational modeling approaches conducted by the

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

International Commission on Radiological Protection (ICRP, 1998) for assessing the effect of autosomal dominant or recessive mutations on radiation-induced tumor frequencies.

However, at the individual level, persons in such susceptible groups face the potential of an increased risk at the individual level. ICRP (1998) in its report Genetic Susceptibility to Cancer concluded:

The principal conclusion by the Commission is that, on current knowledge, the presence of familial cancer disorders does not impose unacceptable distortions in the distribution of radiation cancer risk in typical human populations. For individuals with familial cancer disorders, radiation cancer risks relative to baseline are judged by the Commission to be small at low doses and insufficient to form the basis of special precautions. It seems likely however those risks to those with familial cancer disorders will become important at the high doses received during radiotherapy.

NCRP in its Report 136 (NCRP, 2001, page 194) endorsed the ICRP statement on the effect of susceptibility mutations at the population level:

The studies to date of the rare genetic mutations do not suggest they will have a major impact on total irradiated-population risk or on the shape of the dose-response.

Again, it is the effect at the individual level that would probably be influenced by mutations for susceptibility to radiation-induced cancer at the high doses received during therapy. No information is available on a specific sensitivity to cancer induction by low doses received occupationally, medically, or environmentally of people who carry susceptibility mutations. However, for people with such mutations, exposure to a given dose of radiation might be more likely to induce a cancer but the individual’s baseline risk is also elevated.

In recent years, the approaches for identifying single-nucleotide polymorphisms in the human population have improved substantially (Carlson et al., 2004; Belmont and Gibbs, 2004). In addition, recent studies have provided evidence of links between specific polymorphisms and increased disease outcome (Houlston and Peto, 2004). Such studies do not include radiation-induced cancers. However, given the prevalence of polymorphisms in the population and their relative frequency (over 1% by definition), scientists and risk assessors need to follow the research in this field to determine whether specific genetic polymorphisms can enhance individual risks of radiation-induced tumors.

Minisatellite Alterations and Hereditary Risk

Minisatellites are variable regions of DNA characterized by a series of repeat nucleotide sequences that usually occur in noncoding regions of DNA. Muta-

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

tions in minisatellite regions involve changes in the number of repeat sequences, and they are about 1,000 times more common than base-change mutations that occur in protein-coding genes. Because of their high mutability by ionizing radiation (for example, about 4% in the exposed people discussed in Dubrova et al., 2002a), minisatellite mutations have been proposed for use in measuring hereditary effects of radiation exposure.

Dubrova and colleagues have conducted several studies on populations exposed to fallout from the Chornobyl accident (Dubrova et al., 1996, 1997, 2002b) and on families living in the vicinity of the Semipalatinsk nuclear test site (Dubrova et al., 2002a). They have demonstrated a 1.6- to 2.0-fold increase in minisatellite mutations in the offspring of irradiated parents. However, not only does the increase appear to be independent of the dose received, but also no mechanism has been identified by which radiation could induce such changes in the number of repeats in a particular minisatellite region.

Using a similar technique, Weinberg et al. (2001) reported a 7-fold increase in repeat sequence mutations in people born to fathers who were involved in cleanup at the Chornobyl plant. However, Jeffreys and Dubrova (2001) responded by describing the method used by Weinberg et al. (2001) as unreliable and concluded that the mutants detected had to be validated. That has not been done, so the study by Weinberg et al. (2001) remains controversial.

Other studies of radiation-exposed populations have failed to demonstrate an increase in minsatellite mutations in the offspring of exposed fathers. They include two studies of Chornobyl cleanup workers (Livshits et al., 2001; Kiuru et al., 2001) and a study of the offspring of the Japanese atomic-bomb survivors (Kodaira et al., 1995). In addition, no evidence of increased minisatellite mutations was observed in the sperm of radiotherapy patients sampled at various times after treatment (May et al., 2000).

The UK National Radiological Protection Board (NRPB) has recently commented on the studies conducted at Semipalatinsk by Dubrova et al. (2002a), noting that although all other studies have had negative results or been methodologically flawed, Dubrova et al. (2002a) provides the most convincing demonstration to date of a radiation-induced effect on minisatellite mutation frequency (Bouffler and Lloyd, 2002). However, in concluding that, Bouffler and Lloyd (2002) noted Dubrova et al. (2002a) reported a 1.8-fold increase in minisatellite mutation frequency for doses cited as greater than 1 Sv. That value is broadly consistent with the genetic doubling dose of 1 Sv used by ICRP (1991) and UNSCEAR (2001).

In a recent comprehensive review of the basis and derivation of genetic risks, UNSCEAR (2001) discussed the work of Dubrova and colleagues and concluded that “minisatellite variations very rarely have phenotypic effects.” UNSCEAR did not include data on minisatellite mutations in its genetic risk estimates. Where associations between minisatellite variations and phenotypic effects have been

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

found, they have been for multifactorial diseases whose complex etiology involves multiple genes and interaction with environmental factors. Such diseases are far less responsive to an increase in mutation rate than those due to single gene mutations (UNSCEAR, 2001). Bouffler and Lloyd (2002) concluded that minisatellite mutations are unlikely to affect the incidence of heritable disease substantially.

We can conclude that no new evidence on radiation-induced minisatellite mutations has been published that requires revision of the human heritable risk posed by radiation exposure.

In summary, recent studies in cellular and molecular radiation biology are providing new insights into how radiation interacts with cellular components and how signals can be transferred from “hit” cells to “unhit” ones. The information should improve understanding of the underlying cellular changes that might be involved in the induction of mutations and how the changes are related to an excess risk of cancer or hereditary disorders after radiation exposure. In this context, radiation risk assessments and consequent risk estimates are disease-based. That is, they are derived from the findings of epidemiologic studies of exposed human populations buttressed by the results of experimental studies of irradiated laboratory animals. Thus, they do not rely directly on mechanistic considerations. Furthermore, risk-assessment approaches are supported by information on the dose-response relationships obtained for a variety of mutational end points known to be associated with carcinogenesis and hereditary effects. Reviews by various authoritative international and national scientific bodies of the risks to health arising from exposure to low doses of radiation have included knowledge of potential novel biologic mechanisms; they include the recent NCRP review that led to Report 136 (NCRP, 2001).

None of those reviews concluded that the epigenetic phenomena require modification of the LNT dose-response model that forms the basis of current risk estimates. A move to a more biologically based risk-assessment approach would require consideration of potentially confounding factors for low-dose response. With respect to genetic susceptibility to radiation-induced tumors, the current position of both ICRP and NCRP is that the effect of susceptibility mutations on population risk would be very small. For individual risk, there would be a minor effect of susceptibility mutations at low doses; they might have a much larger effect at the high doses received in therapy. The effect of single-nucleotide polymorphisms on sensitivity to tumor induction by radiation is not known.


Conclusions The committee concludes, on the basis of recent data on radiation-induced responses at the cellular and molecular levels discussed in this section, that current cancer risk estimates do not need revision. That conclusion is also based on the fact that current risk estimates are developed directly from human tumor frequencies.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

The committee further concludes that continued monitoring of research in cellular and molecular radiation biology as related to radiation-induced cancer risk is needed.

RECENT DEVELOPMENTS IN RADIATION DOSIMETRY AND RADIATION DOSE AND RISK ASSESSMENT

Radiation Dosimetry

Estimates of health risks to exposed cohorts in the HRSA program have historically been obtained from dose assessment or retrospective dosimetry. This was necessary because many of the people, in particular downwinders, did not have personal dosimeters and there was a lack of comprehensive workplace or environmental monitoring. Reconstructing the external dose requires information on fallout deposition patterns, life styles, shielding by building materials and dose conversion factors. Reconstructing the dose from internal emitters involves detailed studies of the movement of the deposited radionuclides through the food chain into the body and the resultant organ doses obtained by using physiologically based pharmacokinetic (PBPK) models. Descriptions of these procedures for fallout are presented by Bouville et al. (2002) and Simon and Bouville (2002).

There are continuing efforts to update conversion factors relating radioactivity to dose for both internal and external exposures. Conversion coefficients for external radiation for use in radiologic protection have been revised by ICRP (ICRP, 1996) and the US Environmental Protection Agency (EPA) (Eckerman and Ryman, 1993). A summary of procedures for dose estimation from radionuclides in the environment has also been published by the International Commission on Radiation Units and Measurements (ICRU) (ICRU, 2002). Doses from internally deposited radionuclides were estimated with physiologically based pharmacokinetic (PBPK) models, such as those developed by ICRP (1979). Dose-conversion factors for internal deposition of radionuclides have been revised by EPA (Eckerman et al., 1988).

Tissue weighting factors, wT are defined as the fractions of stochastic risk of carcinogenesis or hereditary effects resulting from radiation exposure of organ T, relative to the total risk posed by uniform exposure of the entire body (ICRP, 1991). The most recent accepted values are shown in Table 3.7. Modifications to wT are being reviewed by ICRP on the basis of the latest assessment of cancer incidence from epidemiologic studies. The wT for the gonads may be reduced by a factor of 5 to 0.04. The value of wT may increase for breast cancer from 0.05 to 0.12. There should be no changes in the wT proposed for thyroid cancer or respiratory cancers. There has been complete revision of the model for the human respiratory tract (ICRP, 1994) and of basic anatomic data on the skeleton (ICRP, 1995).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

Collectively, the revisions in dose-conversion factors and other dosimetry measures should reduce uncertainty in estimates of dose, but they will not substantially change the general assessment of risk to cohorts in the HRSA program.

The revised PBPK model for the human respiratory tract does not include dosimetry for inhalation of radon or the short-lived descendants of radon that are referred to as radon daughters. Historically, the risks posed by radon have been related to the time-integrated concentration of potential alpha energy from short-lived radon daughters, usually expressed in working level month (WLM). The committee does not expect that practice to be revised. Any changes in risk estimates associated with radon will be related to radiation biology or observed cancer incidence rather than to a revised paradigm for dosimetry.

The most comprehensive database of risks associated with external exposure from ionizing radiation is the Life Span Study of Japanese atomic-bomb survivors conducted by the Radiation Effects Research Foundation. Previous estimates of risk were related to dose assessments for each person according to a system called DS86 (NRC, 1987). In 2001, a National Research Council report made recommendations regarding revisions to DS86 to reduce uncertainty in dose assessments (NRC, 2001). The revisions have been completed and will be published as DS02 in 2005. The protocol has been used to obtain revised estimates of dose for each person in the study. The new data indicate that cancer-mortality risk factors (relative risk per unit dose) will decrease by about 8% because of changes in dosimetry. That is principally because of an increase in the gamma-ray dose for both cities. There are, however, no changes in the apparent shape of the dose-response curve or the age and time-since-exposure patterns of risk. Efforts are under way to evaluate and reduce uncertainties in the risk estimates for mortality and to develop risk estimates for cancer incidence (Preston et al., 2004).

The risk of thyroid cancer in people exposed to 131I has now been conclusively demonstrated as a result of the 1986 Chornobyl accident. The Institute of Medicine and National Research Council discussed the early skepticism that met reports of increased thyroid-cancer incidence at Chornobyl and the later findings showing that irradiation of the thyroid by 131I is almost, if not equally, as effective as irradiation by external radiation (IOM-NRC, 1999). Most of the radiation-induced thyroid cancers incurred after that accident are papillary thyroid cancers, the latent period is short, and there are indications that they are more aggressive than usual. Recent findings on the dosimetry of 131I exposure from Chornobyl and its related risk may clarify uncertainties in estimating their health effects.

Radiation Dose and Risk Assessment

National Cancer Institute 1997 131I Study

Since RECA was enacted in 1990, the National Cancer Institute (NCI) has completed a comprehensive study of radiation doses to the thyroid from 131I

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

released from tests at the Nevada Test Site (NTS) (NCI, 1997). The study uses fallout measurements, atmospheric modeling, and statistical analysis to estimate 131I fallout deposition density in each county of the continental United States and the corresponding radiation doses to the thyroid for each atmospheric test at the NTS. NCI took into account the ages of those at risk of exposure and their consumption of milk and other foodstuffs. NCI presented its results in tables and in a series of maps showing the doses in all counties for four milk-consumption rates for people born in selected years from 1930 to 1962; NCI also produced maps showing doses for different test series.

NCI has provided the committee with updated versions of several of the maps, and we present them in this report. The maps show the radiation doses to people by county. They include the latest revisions to the dose calculations and show the doses based on contours. Thus, they offer a more accurate representation than the earlier NCI maps in that the doses are based on where the fallout was deposited and did not stop at county boundaries.

Figure 4.1 shows the estimate of the dose to the thyroid of a child born on January 1, 1951, for average milk consumption. Estimated doses range from less than 1 mGy to greater than 100 mGy. The map gives the total thyroid dose from both external and internal radiation. The great majority of the dose, however, is from the ingestion of 131I in foodstuffs, particularly milk.

The dose to the thyroid from 131I depended significantly on the age of the person when the exposure was received. Because of the relatively higher uptake of iodine in young children and the smaller thyroid, which resulted in a greater

FIGURE 4.1 Geographic distribution of estimated total (external + internal) dose (mGy) from all NTS tests to the thyroid of children born on 1 January 1951 and who were average milk drinkers (map courtesy of National Cancer Institute).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

iodine concentration, the thyroid dose in young children is higher than that in other age groups for the same amount of fallout and the same dietary intake of 131I. The dependence of dose on age at exposure tends to decrease with age until adulthood when dose varies little with age.

Because of the dependence of dose on age at exposure in young children, maps of thyroid doses to people born at other times may differ from Figure 4.1. Such maps—for example, for a person born on January 1, 1954—would reflect the influence of 131I deposited in fallout from tests occurring while that person was a small child.

For comparison, Figure 4.2 shows the thyroid doses from all tests at the NTS to people who were adults during the time of nuclear testing.

Figures 4.1 and 4.2 show that people living in many parts of the United States, not just those living near the NTS, received high thyroid doses as a result of nuclear tests. For example, for children born on January 1, 1951, thyroid doses in areas in Idaho, Montana, and Colorado, were also higher, and thyroid doses in other areas, such as the Midwest and up-state New York and Vermont, were elevated.

Much of the geographic distribution is due to the dynamics of 131I. First, once away from the NTS, 131I is deposited mainly through precipitation (“wet” deposition), so areas that receive precipitation when a fallout cloud is passing overhead are more likely to have high deposition. Second, once it is deposited, the main exposure pathway is ingestion of milk from cattle or goats that grazed on pasture that received the fallout. Consequently, thyroid doses tend to be

FIGURE 4.2 Geographic distribution of estimated total (external + internal) dose (mGy) from all NTS tests to the thyroid of those of adult age at the time of exposure and who were average milk drinkers (map courtesy of National Cancer Institute).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

elevated in areas receiving fallout through wet deposition where entry into the milk pathway is possible.

On the basis of the 1997 study (NCI, 1997), NCI developed a 131I dose calculator that was published on the Web at http://ntsi131.nci.nih.gov/. The user supplies date of birth, sex, locations and dates of residence, and milk-consumption pattern. The calculator then uses the results of the 1997 study to estimate the thyroid dose from 131I and its 90% credibility interval.

Institute of Medicine-National Research Council Review of 1997 National Cancer Institute 131I Study

The NCI 131I study was reviewed by an Institute of Medicine-National Research Council committee in 1999 (IOM-NRC, 1999). That committee stated that the NCI approach was generally reasonable, but found that the county-specific estimates of thyroid dose were too uncertain to be useful in estimating individual doses.

Individual doses depend strongly on specific variables, such as age at exposure and amount of milk consumed, which are not considered in the county doses. Estimating individual doses is possible but highly uncertain because important data are not available or are of questionable reliability. The committee also observed that there was little epidemiologic evidence of a widespread increase in thyroid cancer.

Centers for Disease Control and Prevention-National Cancer Institute 2001 Draft Feasibility Study

In 2001, the Centers for Disease Control and Prevention (CDC) and NCI published a draft feasibility study of the health consequences of nuclear-weapons testing on the American population (CDC-NCI, 2001). The report considered all radionuclides that contributed substantially to the radiation dose, and estimated the effective dose and the dose equivalent to the organs at risk. Both NTS fallout and global fallout were considered. Global fallout included not only the fallout from American tests but also the contribution from tests of other nations. The draft feasibility study concluded that a full dose assessment was possible but that it would be a major effort comparable with the NCI 131I study discussed above.

The CDC-NCI study used the 131I fallout deposition densities found in the 1997 NCI study as a starting point to calculate the deposition densities from NTS fallout of the 33 other radionuclides that contributed substantially to the radiation dose. The study then calculated the doses from both internal and external exposure to those radionuclides. Only the dose to the thyroid from 131I resulted in an internal radiation dose that substantially exceeded the dose from external radiation. As a result, most organ doses (except to the thyroid) were roughly the same.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

NCI has prepared updated maps showing the current best estimates of dose to various organs and made them available to the committee. The maps are used in this report rather than the original maps in the 2001 draft feasibility study. In Figures 4.3 and 4.4, the dose to the red bone marrow from nuclear tests at the NTS is shown as representative of the other organ doses for an adult and a child born on January 1, 1951.

Both the 1997 NCI study and the 2001 CDC-NCI draft feasibility study estimated doses to the thyroid from 131I at the NTS. Although the study results are similar, they are not identical. The difference is discussed briefly in the 2001 report and attributed to differences in estimating the amount of fallout retained by vegetation. In addition, the 2001 results are preliminary in that they are for the draft feasibility study, and did not include uncertainties.

In addition to estimates of doses from NTS fallout, the 2001 draft feasibility study evaluated doses from global fallout. The doses to red bone marrow were found to be slightly higher from global fallout than from NTS fallout but less for the thyroid.

The 2001 CDC-NCI draft feasibility study presents maps similar to Figures 4.3 and 4.4 for global-fallout red marrow doses by county in the United States (CDC-NCI, 2001). The study did not estimate the 131I doses to the thyroid from global fallout by county (although some 131I was occasionally present), because of lack of data. The 131I doses were given for the United States as a whole. Doses from 3H and 14C, which affect the hydrological and carbon cycles, respectively,

FIGURE 4.3 Geographic distribution of estimated total (external + internal) dose (mGy) from all NTS tests to the red bone marrow of children born on 1 January 1951 (map courtesy of National Cancer Institute).

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×

FIGURE 4.4 Geographic distribution of estimated total (external + internal) dose (mGy) from all NTS tests to the red bone marrow of those of adult age at the time of exposure (map courtesy of National Cancer Institute).

were also estimated for the United States as a whole. The report notes that the proportion of global fallout due to US weapons testing can be roughly determined from the fission yield of the US tests relative to the total fission yield from all high-yield nuclear testing.

National Research Council Review of Centers for Disease Control and Prevention-National Cancer Institute 2001 Draft Feasibility Study

The study was reviewed by a National Research Council committee that published its report in 2003 (NRC, 2003c). Among its conclusions and recommendations, the National Research Council found the following:

  • The 131I fallout data and the resulting dose and thyroid-cancer risk should be reanalyzed to include the new dosimetry and risk estimates from Chornobyl to update the 1997 NCI report.

  • On the basis of the results of the draft feasibility study, further work with fallout radionuclides other than 131I would not be warranted, because of the very low levels of associated exposure and the uncertainties in their distribution over time and location.

  • In agreement with the authors of the draft feasibility study, the dose and risk estimates that were presented were developed as population averages and should not be used to estimate risks to specific individuals.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
  • A program should be established to examine and archive fallout-related documents from sites operated by the Department of Energy and the Department of Defense and other relevant sites.

National Cancer Institute and Centers for Disease Control and Prevention Working Group 2003 Revision of NIH Radioepidemiology Tables

An NCI and CDC working group (NCI-CDC, 2003) reviewed and revised the 1985 National Institutes of Health radio-epidemiology tables (NIH, 1985). The revision was principally based on the 1958–1987 Life Span Study Tumor Registry data on the atomic-bomb survivors at Hiroshima and Nagasaki. The computer program Interactive Radio-Epidemiological Program (IREP, version 5.3) incorporated the results of this work to give probability of causation/assigned share values for individual radiation exposures.

Risk coefficients and associated PC/AS values in some cases have been substantially changed, both from the original NIH tables and from their 1988 revision by the Committee on Interagency Radiation Research and Policy Coordination (CIRRPC) (CIRRPC, 1988). The NCI-CDC report used cancer-incidence data on the atomic-bomb survivors, rather than the cancer mortality data on most cancers used for the 1985 report. For thyroid cancer, the NCI-CDC report used a compilation of seven studies (Ron et al., 1995), which was considerably more extensive than that used by the NIH report.

CIRRPC also assumed that, for a particular cancer, an applicant had a low baseline risk at the 10th percentile of the cancer risk distribution and that the ERR varied inversely with the baseline risk. The NCI-CDC revision did not use those assumptions, which had accounted for a factor of two increase in the ERR for most cancers (NCI-CDC, 2003).

CONCLUSION

This chapter has presented the results of recent studies in radiation epidemiology, biology, and dosimetry. The overall aim is to develop a database that forms part of the consideration of new populations or geographic areas for coverage by RECA. Chapters 5 and 6 consider the issue of additions to RECA.

Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 73
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 74
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 75
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 76
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 77
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 78
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 79
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 80
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 81
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 82
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 83
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 84
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 85
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 86
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 87
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 88
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 89
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 90
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 91
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 92
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 93
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 94
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 95
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 96
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 97
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 98
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 99
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 100
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 101
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 102
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 103
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 104
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 105
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 106
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 107
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 108
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 109
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 110
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 111
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 112
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 113
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 114
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 115
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 116
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 117
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 118
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 119
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 120
Suggested Citation:"4 Review of Recent Data on Radiation Epidemiology, Biology, and Dosimetry." National Research Council. 2005. Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program. Washington, DC: The National Academies Press. doi: 10.17226/11279.
×
Page 121
Next: 5 Expanding RECA Eligibility: Scientific Issues »
Assessment of the Scientific Information for the Radiation Exposure Screening and Education Program Get This Book
×
Buy Paperback | $85.00 Buy Ebook | $69.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

The Radiation Exposure Compensation Act (RECA) was set up by Congress in 1990 to compensate people who have been diagnosed with specified cancers and chronic diseases that could have resulted from exposure to nuclear-weapons tests at various U.S. test sites. Eligible claimants include civilian onsite participants, downwinders who lived in areas currently designated by RECA, and uranium workers and ore transporters who meet specified residence or exposure criteria. The Health Resources and Services Administration (HRSA), which oversees the screening, education, and referral services program for RECA populations, asked the National Academies to review its program and assess whether new scientific information could be used to improve its program and determine if additional populations or geographic areas should be covered under RECA. The report recommends Congress should establish a new science-based process using a method called "probability of causation/assigned share" (PC/AS) to determine eligibility for compensation. Because fallout may have been higher for people outside RECA-designated areas, the new PC/AS process should apply to all residents of the continental US, Alaska, Hawaii, and overseas US territories who have been diagnosed with specific RECA-compensable diseases and who may have been exposed, even in utero, to radiation from U.S. nuclear-weapons testing fallout. However, because the risks of radiation-induced disease are generally low at the exposure levels of concern in RECA populations, in most cases it is unlikely that exposure to radioactive fallout was a substantial contributing cause of cancer.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!