. "Report Contents." Health Risks from Exposure to Low Levels of Ionizing Radiation BEIR VII, Phase I, Letter Report. Washington, DC: The National Academies Press, 1998.
The following HTML text is provided to enhance online
readability. Many aspects of typography translate only awkwardly to HTML.
Please use the page image
as the authoritative form to ensure accuracy.
NATIONAL RESEARCH COUNCIL
COMMISSION ON LIFE SCIENCES
2101 Constitution Avenue Washington, D.C. 20418
BOARDONRADIATIONEFFECTSRESEARCH
NAS Room 342
TEL: (202) 334-2232 FAX: (202) 334-1639
January 21, 1998
Dr. Jerome Puskin
US Environmental Protection Agency
Radiation Studies Branch
401 M Street, SW Washington, DC 20460
Dear Dr. Puskin:
The Environmental Protection Agency Office of Radiation and Indoor Air asked the National Research Council to evaluate whether sufficient new data exist to warrant a reassessment of health risks reported in Health Effects of Exposure to Low Levels of Ionizing Radiations (BEIRV) in 1990. To respond to this request, the National Research Council assembled the Committee on Health Risks of Exposure to Low Levels of Ionizing Radiations. The work of the committee was conducted in what was called the BEIR VII phase 1 study. To assist the committee during its deliberations, various scientists were consulted for advice, and a workshop on the impact of biology on risk assessment was held in collaboration with the Department of Energy Office of Health and Environmental Research. The intent of the workshop was to address the implications of new understanding of the biologic basis of radiation injury and carcinogenesis for risk assessment. Through this letter, we are providing you in advance a summary report of the committee 's recommendations. This is being done in order to enable you to begin to move forward as soon as possible in making a decision on the appropriateness of undertaking additional study of the subject.
The National Research Council is the principal operating agency ofthe National Academy of Sciences and the National Academy of Engineeringto serve government and other organizations
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole. Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 1
NATIONAL RESEARCH COUNCIL
COMMISSION ON LIFE SCIENCES
2101 Constitution Avenue Washington, D.C. 20418
BOARD ON RADIATION EFFECTS RESEARCH
NAS Room 342
TEL: (202) 334-2232 FAX: (202) 334-1639
January 21, 1998
Dr. Jerome Puskin
US Environmental Protection Agency
Radiation Studies Branch
401 M Street, SW Washington, DC 20460
Dear Dr. Puskin:
The Environmental Protection Agency Office of Radiation and Indoor Air asked the National Research Council to evaluate whether sufficient new data exist to warrant a reassessment of health risks reported in Health Effects of Exposure to Low Levels of Ionizing Radiations (BEIR V) in 1990. To respond to this request, the National Research Council assembled the Committee on Health Risks of Exposure to Low Levels of Ionizing Radiations. The work of the committee was conducted in what was called the BEIR VII phase 1 study. To assist the committee during its deliberations, various scientists were consulted for advice, and a workshop on the impact of biology on risk assessment was held in collaboration with the Department of Energy Office of Health and Environmental Research. The intent of the workshop was to address the implications of new understanding of the biologic basis of radiation injury and carcinogenesis for risk assessment. Through this letter, we are providing you in advance a summary report of the committee 's recommendations. This is being done in order to enable you to begin to move forward as soon as possible in making a decision on the appropriateness of undertaking additional study of the subject.
The National Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering to serve government and other organizations
OCR for page 2
The following is a synopsis of the conclusions of the BEIR VII phase 1 study:
In the committee's judgment, information that has become available since publication of the 1990 Health Effects of Exposure to Low Levels of Ionizing Radiations (BEIR V) makes this an opportune time to proceed with BEIR VII phase 2 –a comprehensive reanalysis of health risks associated with low levels of ionizing radiations. Such a study should begin as soon as possible and is expected to take about 36 months to complete.
The committee based that judgment on the following considerations:
Substantial new epidemiologic evidence has accumulated since the 1990 BEIR V report was published. The present committee's phase 1 report will cite 39 new epidemiologic studies that fall into this category (see Table 1). Additional studies that have a direct bearing on the subject should become available in the next 3 years, the estimated period required to complete the phase 2 study.
Some of the new epidemiologic data are on subjects on which information had been sparse, such as cancer mortality in those exposed to whole-body irradiation in childhood.
Studies of carcinogenesis completed since publication of the last BEIR report have focused on mechanisms and the cellular and molecular events that are involved in the neoplastic process. The understanding of molecular events involved in carcinogenesis has increased significantly. Mechanisms that might be involved in radiation carcinogenesis have been identified. Further knowledge of these mechanisms that should become available in the next 3 years might affect estimation of the radiation-response curve at low doses.
Over the next few years, investigators will be applying two closely linked approaches using animal models of carcinogenesis. These will likely contribute to a
OCR for page 3
better understanding of mechanisms of radiation-induced cancer. In the first of these two approaches, genetically engineered mice having alterations in specific genes will be used to determine the influence of these genes on the susceptibility of the mice to radiation-induced cancer. In the second approach, studies will be conducted of the inherent differences in susceptibility to radiation-induced cancer among different mouse strains, the objective being to identify the genes involved in controlling susceptibility. Researchers responsible for this new generation of animal studies are taking advantage of the current rapid developments in molecular genetics. Progress on both approaches should be substantial over the next few years. Significant results of relevance to risk estimation are expected to be available for the proposed BEIR VII phase 2 study.
Evidence regarding specific biologic events that can affect the shape of the dose-response curve at low doses is also accumulating. Information on such phenomena as DNA repair, signal transduction, chromosomal instability, and adaptation, although preliminary, might eventually affect risk analyses of low-dose and low-dose-rate exposures.
The committee recommends that the group responsible for the proposed phase 2 study
Include a comprehensive review of all relevant epidemiologic data related to low-LET (low linear energy transfer), i.e. sparsely ionizing, radiation.
Define and establish principles on which quantitative analyses can be based, including requirements for epidemiologic data and cohort characteristics. In this respect, the group should consider biologic factors (such as the dose and dose-rate effectiveness factor, relative biologic effectiveness, genomic instability, and adaptive responses) and appropriate models (favoring simple as opposed to complex models) to develop etiologic models, estimate population detriment, and attribute causation in specific cases.
OCR for page 4
Assess the current status and relevance to risk models of biologic data and models of carcinogenesis. This should include a critical assessment of all data that might affect the shape of the response curve at low doses, in particular, evidence of thresholds or the lack thereof in dose-response relationships and the influence of adaptive responses and radiation hormesis.
Consider potential target cells and problems that might exist in determining dose to the target cell.
Consider any recent evidence regarding genetic effects not related to cancer. Any such data, even if obtained from high radiation exposures or at high dose rates, should be considered.
With respect to modeling, the committee recommends that the group responsible for the proposed phase 2 study
Develop appropriate risk models for major cancer types and other outcomes, including benign disease and genetic effects. Specifically, the responsible group should develop models appropriate for probability-of-causation tables and should consider the fitting of purely empirical models to original data from studies or combined studies, the fitting of purely empirical models with meta-analytic techniques, and the fitting of semiempirical biology-based models to epidemiologic data.
Provide examples of specific risk calculations based on the models and explain the appropriate use of the risk models.
Describe and define the limitations and uncertainties of the risk models and their results. The group conducting the proposed phase 2 study should be directed to develop
OCR for page 5
best-risk estimates as opposed to developing conservative models for purposes of radiation protection.
Discuss the role and effect of modifying factors, including host (such as individual susceptibility and variability, age, and sex), environment, and lifestyle.
Identify critical gaps in knowledge that should be filled by future research.
To accomplish the above charge, the membership of the group responsible for the proposed BEIR VII phase 2 study will require expertise in epidemiology, biostatistics, radiation physics and dosimetry, molecular biology, risk assessment, cancer modeling, animal and cellular radiation biology, somatic cell genetics, cell-cycle regulation and apoptosis, and ionizing radiation-induced DNA damage and its repair. The committee recommends that the experts chosen have adequate resources and access to data for the computing, statistical analyses, and modeling required to complete the study.
We trust that this synopsis of the recommendations of the committee will meet your current needs. The complete report of the committee will be published and provided to your office when it has received the committee's final approval and has been subjected to the National Research Council peer-review process.
Sincerely,
Richard B. Setlow, Ph.D.
Chairman, Committee on Health Effects of Exposure to Low
Levels of Ionizing Radiations (BEIR VII Phase 1)
OCR for page 6
Table 1 is a summary of the more important epidemiologic data that have been published since the 1990 publication of the BEIR V report. Included are studies that are expected to provide new and useful data during the 3-year term of the proposed BEIR VII, Phase II, study. Although not exhaustive, the list should serve as a guide to some of the pertinent new and upcoming epidemiologic data on the subject.
OCR for page 7
Table 1. Summary of Epidemiologic Studies of Low-LET Ionizing Radiation and Cancer, 1990
STUDY
REFERENCE
TYPE OF STUDY
SERIES
SEX
NO. IN STUDY
YEARS OF FOLLOW-UP
CANCER SITES REPORTED
Ankylosing spondylitis patients
Weiss et al. Cancer mortality following x-ray treatment for ankylosing spondylitis. Int J Cancer 1994;59:327-338.
Cohort
Mortality
Male and Female
15,577
1935-1992
All cancer and multiple cancer sites
Weiss et al. Leukemia mortality after x-ray treatment for ankylosing spondylitis. Rad Res 1995;142:1-11.
Cohort
Mortality
Male and Female
14,767
1935-1992
Leukemia
Atomic-bomb survivors
Preston et al. Cancer incidence in atomic-bomb survivors. Part III: leukemia, lymphoma, and multiple myeloma 1950-1987. Rad Res 1994;137:568-597 (2 suppl).
Cohort
Incidence
Male and Female
93,696
1950-1987
Leukemia, lymphoma, multiple myeloma
Thompson et al. Cancer incidence in atomic-bomb survivors. Part II: solid tumors, 1958-1987. Rad Res 1994;137:517-567.
Cohort
Incidence
Male and Female
79,972
1958-1987
Multiple cancer sites (solid tumors)
Ron et al. Incidence of benign gastrointestinal tumors among atomic-bomb survivors. Amer J Epi 1995;142:68-75.
Cohort
Incidence
Male and Female
80,311
1958-1989
Benign tumors of stomach, colon, and rectum
Pierce et al. Studies of the mortality of atomic bomb survivors. Report 12, Part 1. Cancer:1950-1990. Rad Res 1996;146:1-27.
Cohort
Mortality
Male and Female
86,572
1950-1990
Non leukemias, leukemia, and multiple cancer sites
Atomic-bomb survivors (case-control study)
Land et al. A case control interview study of breast cancer among Japanese A-bomb survivors. I. Main effects. Cancer Causes and Control 1994;5:157-169.
Case-control
Female
Cases: 196 Controls: 566
1955-1981
Breast cancer
Land et al. A case-control interview study of breast cancer among Japanese A-bomb survivors. II. Interactions with radiation dose. Cancer Causes and Control 1994;5:167-176.
Atomic-bomb survivors (in utero cohorts)
Delongchamp et al. Cancer mortality among atomic-bomb survivors exposed in utero or as young children, October 1950-May 1992. Rad Res 1997;147:385-395.
Cohort
Mortality
Male and Female
17,601
1950-1992
Non leukemias, leukemia, and multiple cancer sites
OCR for page 8
Canadian fluoroscopy
Howe. Lung Cancer Mortality between 1950 and 1987 Following Exposure to fractionated moderate dose rate ionizing radiation in the Canadian Fluoroscopy Study and a comparison with lung cancer mortality in the Atomic Bomb Survivors Study. Radiat Res 1995; 142:295-304.
Cohort
Mortality
Male and Female
64,172
1950-1987
Lung cancer
Howe and McLaughlin. Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate dose rate ionizing radiation in the Canadian fluoroscopy study and a comparison with breast cancer mortality in the Atomic bomb survivors study. Rad Res 1996;145:694-707.
Cohort
Mortality
Female
31,917
1950-1987
Breast cancer
Cervical cancer patients
Kleinerman et al. Second primary cancer after treatment for cervical cancer. Cancer 1995;76:442-452.
Cohort
Incidence
Female
86,193
1935-1990
Multiple cancer sites
Contralateral breast (Denmark)
Storm et al. Adjuvant radiotherapy and risk of contralateral breast cancer. J Nat Cancer Inst 1992;84:1245-1250.
Case-control in a cohort
Female
Cohort: 56,540
Cases: 691
Controls: 691
1943-1986
Breast cancer
Contralateral breast (U.S.A.)
Boice et al. Cancer in the contralateral breast after radiotherapy for breast cancer. N Engl J Med 1992;326:781-785.
Case control within a cohort
Female
Cohort: 4,109
Cases: 655
Controls: 1,189
1935-1987
Breast cancer
Fallout from Nevada Test Site
Kerber et al. A cohort study of thyroid disease in relation to fallout from nuclear weapons testing. JAMA 1993;270:2076-2082.
Cohort
Incidence
Male and Female
2,473
1965-1986
Thyroid cancer and other thyroid disease
Simon et al. The Utah leukemia case-control study: dosimetry methodology and results. Hlth Phys 1995;6814:460-471.
Case-Control
Male and Female
Cases: 1,177
Controls: 5,330
1952-1981
Leukemia
Massachusetts fluoroscopy
Davis et al. Cancer mortality in a radiation-exposed cohort of Massachusetts tuberculosis patients. Cancer Res 1989;49:6130-6136.
Cohort
Mortality
Male and Female
13,385
1929-1986
Multiple cancer sites
Boice et al. Frequent chest x-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts. Rad Res 1991;125:214-222.
Cohort
Incidence
Female
4,940
1925-1986
Breast cancer
OCR for page 9
Multiple diagnostic x-rays of scoliosis patients
Hoffman et al. Breast cancer in women with scoliosis exposed to multiple diagnostic x-rays. J Natl Cancer Inst 1989;81:1307-1312.
Cohort
Incidence
Female
1,030
1935-1986
Breast cancer
Nuclear industry workers (combined analysis)
Cardis et al. Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries. Rad Res 1995;142:117-132.
Cohort
Mortality
Male and Female
95,673
1943-1988
Multiple cancer sites
Cardis et al. Direct estimates of cancer mortality due to low doses of radiation: an international study. Lancet 1994;344:1039-1043.
Cohort
Mortality
Male and Female
95,673
1943-1988
Solid tumors and leukemia
Nuclear workers at Mayak Production Association
Koshurnikova et al. NCRP Proceedings, 1996, 113:T2, 113-122.
Cohort
Mortality
Male and Female
18,879
1948-1993
Lung cancer and leukemia
Pelvic radiotherapy for benign gynecologic disease
Inskip et al. Leukemia, lymphoma and multiple myeloma after pelvic radiotherapy for benign disease. Rad Res 1993;135:108-124.
Cohort
Mortality
Female
12,955
1929-1985
Multiple hematopoietic cancers
Pooled analysis of external radiation and thyroid cancer
Ron et al. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Rad Res 1996;141:259-277.
Cohort Case-control
Incidence
Male and Female
120,000
1926-1990
Thyroid cancer
Radiation treatment for benign head and neck conditions (benign thyroid tumors)
Wong et al. Benign thyroid tumors: general risk factors and their effects on radiation risk estimation. Amer J Epi 1996;144:728-733.
Cohort
Incidence
Male and Female
544
1939-1991
Benign thyroid nodules
Radiation treatment for benign head and neck conditions (thyroid cancer and thyroid nodules)
Schneider et al. Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the prolonged effects of radiation on the thyroid. J Clin Endocrinol Metab 1993;77:362-269.
Cohort
Incidence
Male and Female
4,296
1939-1990
Thyroid cancer and nodules
Radiation treatment for breast cancer
Curtis et al. Risk of leukemia after chemotherapy and radiation treatment for breast cancer. N Engl J Med 1992;326:1745-1751.
Case-control within cohort
Female
Cohort: 82,700
Cases: 90
Controls: 264
1973-1985
Leukemia
Radiation treatment for peptic ulcer
Griem et al. Cancer following radiotherapy for peptic ulcer. J Natl Cancer Inst 1994;86:842-849.
Cohort
Mortality
Male and Female
3,609
1937-1985
Multiple cancer sites
OCR for page 10
Radiotherapy treatment for Hodgkin's Disease (breast cancer)
Hancock et al. Breast cancer after treatment of Hodgkin's Disease. J Natl Cancer Inst 1993;85:25-31.
Cohort
Incidence and Mortality
Female
885
1961-1990
Breast cancer
Radiotherapy treatment for Hodgkin's Disease (gastro intestinal cancer)
Birdwell et al. Gastrointestinal cancer after treatment of Hodgkin 's Disease. Int J Rad Oncol Biol Phys 1997;37:67-73.
Cohort
Incidence and Mortality
Male and Female
2,441
1961-1993
Multiple cancer sites (gastrointestinal only)
Radiotherapy treatment for metropathia hemorrhagic anemia
Darby et al. Mortality in a cohort of women given x-ray therapy for metropathia hemorrhagica. Int J Cancer 1994;56:793-801.
Cohort
Mortality
Female
2,067
1940-1991
Multiple cancer sites
Radiotherapy treatment for pituitary adenoma
Brada et al. Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma. Br Med J 1992;304:1343-1346.
Cohort
Incidence
Male and Female
334
1962-1986
Multiple cancer sites (solid tumors only)
Radiotherapy treatment for skin, hemangioma in childhood
Furst et al. Tumors after radiotherapy for skin hemangioma in childhood. Act Oncologica 1990; 29:557-562.
Case-control within a cohort
Male and Female
Cohort: 14,647
Cases: 94
Controls: 359
1920-1986
Multiple cancer sites (solid tumors)
Radiotherapy treatment for thymus enlargement
Shore et al. Overview of radiation induced skin cancer in humans. Int J Radiat Biol 1990;57:809-827.
Cohort
Incidence
Male and Female
7,450
1953-1989
Skin cancer
Radiotherapy treatment for uterine bleeding
Inskip et al. Cancer mortality following radium treatment for uterine bleeding. Rad Res 1990;123:331-344.
Cohort
Mortality
Female
4,153
1925-1984
Multiple cancer sites
Tinea capitis (Israel)
Ron et al. Thyroid neoplasia following low-dose radiation in childhood. Rad Res 1989;120:516-531.
Cohort
Incidence
Male and Female
10,834
1950-1986
Thyroid cancer and other thyroid disease
Ron et al. Radiation induced skin carcinomas of the head and neck. Rad Res 1991;125:318-329.
Cohort
Incidence
Male and Female
27,060
1950-1980
Melanoma, other skin cancer and benign skin tumors
Women treated for infertility
Ron et al. Mortality following radiation treatment for infertility of hormonal origin or amenorrhea. Int J Cancer 1994; 23:1165-1173
Cohort
Mortality
Female
816
1925-1991
Multiple cancer sites
OCR for page 11
STUDY
REFERENCE
DESCRIPTION
In utero exposure
Doll and Wakeford. Risk of childhood cancer from fetal irradiation, Brit J Radiol 1997; 70:130-139
A review of case-control and cohort studies of childhood cancers.
