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Veterans and Agent Orange: Update 2004
6
Cancer
Cancer is the second leading cause of death in the United States. Among men aged 45–64, the group that includes most Vietnam veterans, the risk of dying from cancer nearly equals the risk of dying from heart disease, the main cause of death in the United States (US Census, 1999). In 2004, about 563,700 Americans are expected to die from cancer—more than 1,500 people per day. In the United States, one of every four deaths is from cancer (ACS, 2004a).
In this chapter, the Veterans and Agent Orange: Update 2004 committee summarizes and reaches conclusions about the strength of the evidence from epidemiologic studies regarding associations between exposure to the compounds of interest (2,4-dichlorophenoxyacetic acid [2,4-D]; 2,4,5-trichlorophenoxyacetic acid [2,4,5-T] or its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]; picloram; cacodylic acid) and each type of cancer under consideration in the report. For any new study that reports on just a single type of cancer and that does not revisit a previously studied population, its design information is summarized here with its results; design information for all other new studies can be found in Chapter 4, and tables that summarize the major studies are in Appendix A. The cancer types are, with minor exceptions, discussed in the order in which they are listed in the International Classification of Diseases, Ninth Edition (ICD-9). ICD-9 is the classification used to code and classify mortality data from death certificates. ICD-9 CM (clinical modification) is used to code and classify morbidity data from medical records, hospital records, and surveillance surveys. Appendix C lists ICD-9 codes (and corresponding ICD-10 codes) for the major forms of cancer. The categories of association and the committee’s approach to categorizing the health outcomes are discussed in Chapters 1 and 2.
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In assessing a possible connection between herbicide exposure and risk of cancer, one important issue is the magnitude of exposure for the people included in a study. As noted in Chapter 5, there is a great variety in detail and accuracy of exposure assessment among the studies the committee reviewed. A small number used biologic markers of exposure, such as the presence of a compound in serum or tissues; some developed an index of exposure from employment or activity records; others used surrogate measures of exposure, such as being present when herbicides were used. Inaccurate assessment of exposure can obscure the presence or absence of exposure–disease associations and thus make it less likely that a true risk will be identified.
In this chapter, background information about each cancer, including data on its incidence in the general US population, is followed by a summary of the findings described in the previous Agent Orange reports (Veterans and Agent Orange, hereafter referred to as VAO [IOM, 1994]; Veterans and Agent Orange: Update 1996, hereafter, Update 1996 [IOM, 1996]; Veterans and Agent Orange: Update 1998, hereafter, Update 1998 [IOM, 1999]; Veterans and Agent Orange: Update 2000, hereafter, Update 2000 [IOM, 2001]; and Veterans and Agent Orange: Update 2002, hereafter, Update 2002 [IOM, 2003]), a discussion of the most recent scientific literature, and a synthesis of the material reviewed. Where appropriate, the literature is discussed by exposure type (occupational, environmental, service in Vietnam). Each section ends with the committee’s conclusion regarding the strength of the evidence from epidemiologic studies, biologic plausibility, and evidence regarding epidemiology and Vietnam veterans.
Cancer incidence data for the general US population are included in the background sections to provide a context for consideration of cancer risk in Vietnam veterans. Incidences are reported for people 50–64 years old because most Vietnam-era veterans are in this age group. The data, which were collected for the Surveillance, Epidemiology, and End Results (SEER) Program of the National Institutes of Health—National Cancer Institute, are categorized by sex, age, and race, all of which can have a profound effect on risk. Prostate cancer incidence, for example, is approximately 4.4 times higher in men between the ages of 60 and 64 than it is in men 50–54 years old; it is approximately twice as high in blacks 50–64 years old as it is in whites in the same age group (NCI, 2004). The figures presented for each cancer are estimates for the entire US population, not predictions for the Vietnam-veteran cohort. Many factors can influence incidence, among them personal behavior (tobacco use, diet), genetic predisposition, and medical history. Those factors can make someone more or less likely than average to contract a given cancer. Incidence data are reported for all races and also separately for blacks and whites. The data reported are for 1997–2001, the most recent data set available to the committee.
Incidence figures given here are not directly comparable to the figures listed in earlier Updates. Earlier reports used 1990 US Census data; this report used data from the 2000 Census, so some of the differences in incidence estimates
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resulted from changes in demographics rather than from changes in the factors that determine cancer rates.
There is still considerable uncertainty about the magnitude of potential risk posed by exposure to the compounds of interest as shown by the occupational, environmental, and veterans’ studies reviewed by the committee. Many of those studies provided inadequate controls for important confounders, and there is not enough information to extrapolate from exposure as presented in those studies to that of individual Vietnam veterans. The committee therefore cannot measure the likely risk to Vietnam veterans that is attributable to exposure to the compounds of interest in Vietnam. Where the data permit, qualitative observations are offered.
Information about biologic mechanisms that could contribute to carcinogenic activity by any of the agents of interest is summarized in the Biologic Plausibility section at the conclusion of this chapter. It distills toxicologic information concerning how any of the chemicals of interest impact general mechanisms of carcinogenesis, which is presented in detail in Chapter 3. Such information, of course, applies to all the cancer sites discussed individually in this chapter. When biologic plausibility is addressed for a particular site, the generic information is implicit, and only toxicologic information specific to carcinogenesis at the site in question is presented.
GASTROINTESTINAL TRACT CANCERS
Gastrointestinal tract tumors are among the most common of cancers. The committee reviewed data on esophageal cancer (ICD-9 150.0–150.9), stomach cancer (ICD-9 151.0–151.9), pancreatic cancer (ICD-9 157.0–157.9), colon cancer (ICD-9 153.0–153.9), and rectal cancer (ICD-9 154.0–154.9). According to American Cancer Society (ACS) estimates, about 255,640 people will be diagnosed with those cancers in the United States in 2004, and 134,840 people will die from them (ACS, 2004a). Colon cancer accounts for about 40% of those diagnoses and deaths. Collectively, gastrointestinal tract tumors are expected to account for 19% of new diagnoses and 24% of cancer deaths in 2004. Colorectal cancer is the third most common form of cancer in men and in women, excluding basal- and squamous-cell skin cancers. The average annual incidences for gastrointestinal cancers are shown in Table 6-1.
Carcinoma of the esophagus has great geographic variation. The region of the world extending from Iran through the steps of Central Asia, Mongolia, and northern portion of China has cancer frequencies that are 10 times those of the rest of the world. In northern China, the incidence is 160 cases per 100,000, compared with 4–8 per 100,000 in North America, Europe, Southeast Asia, and Japan. In addition to a different disease incidence, there is a difference in the histopathologic type of cancer; squamous-cell carcinoma is predominant in the high-endemic areas, adenocarcinoma makes up approximately 50% of cases in the low-incidence areas of the United States, Europe, Southeast Asia, and Japan.
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TABLE 6-1 Average Annual Incidence (per 100,000) of Selected Gastrointestinal Cancers in United Statesa
50–54 Years of Age
55–59 Years of Age
60–64 Years of Age
All Races
White
Black
All Races
White
Black
All Races
White
Black
Stomach
Males
9.7
8.7
17.3
16.4
14.9
20.9
27.1
22.7
47.4
Females
4.6
3.5
8.8
6.8
5.8
9.3
10.8
8.6
19.0
Esophagus
Males
9.7
9.0
20.6
16.8
16.1
31.2
24.8
24.7
35.5
Females
1.5
1.2
5.1
3.3
2.7
9.0
5.8
5.0
16.4
Colon (excluding the rectum)
Males
33.3
31.1
53.6
59.4
58.7
82.4
105.7
102.8
148.5
Females
27.5
25.4
41.0
44.6
41.6
74.5
78.2
77.5
111.4
Rectum and rectosigmoid junction
Males
23.3
22.2
24.1
36.9
36.8
34.7
55.1
54.2
58.7
Females
14.0
13.3
17.5
22.0
21.2
30.6
29.6
30.3
35.0
Pancreas
Males
12.7
12.1
22.5
20.3
18.8
34.7
33.7
33.4
48.4
Females
7.7
7.5
11.3
13.6
12.7
21.3
24.0
22.5
38.0
a SEER (Surveillance, Epidemiology, and End Results Program) nine standard registries, crude age-specific rates, 1997–2001.
The incidences of stomach, colon, rectal, and pancreatic cancers increase with age in people 50–64 years old. In general, incidence is higher in men than it is in women, and is higher in blacks than in whites. Other risk factors for those cancers vary but always include family history of the same form of cancer, some diseases of the affected organ, and dietary factors. Tobacco use is a risk factor for pancreatic cancer that might also increase the risk of stomach cancer (Miller et al., 1996). Infection with the bacterium Helicobacter pylori increases the risk of stomach cancer. Type 2 diabetes is associated with an increased risk of cancers of the colon and pancreas (ACS, 2004a).
Summary of VAO, Update 1996, Update 1998, Update 2000, and Update 2002
The committee responsible for VAO concluded that there was limited or suggestive evidence of no association between exposure to the compounds of interest and gastrointestinal tumors. Additional information available to the committees responsible for Update 1996, Update 1998, Update 2000, and Update 2002 did not change that finding. Tables 6-2, 6-3, 6-4, 6-5, and 6-6 summarize the results of the relevant studies.
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TABLE 6-2 Selected Epidemiologic Studies—Stomach Cancer
Reference
Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
OCCUPATIONAL
New Studies
Bodner et al., 2003
Dow chemical production workers—mortality
—
1.5 (0.7–2.7)
Swaen et al., 2004
Dutch licenced herbicide applicators—mortality
3
0.4 (0.1–1.3) b
Studies Reviewed in Update 2002
Burns et al., 2001
Dow 2,4-D production workers—cancer of the digestive organs—mortality
16
0.7 (0.4–1.2)
Studies Reviewed in Update 2000
Steenland et al., 1999
US chemical production workers
13
1.0 (0.6–1.8)
Hooiveld et al., 1998
Dutch chemical production workers
3
1.0 (0.2–2.9)
Rix et al., 1998
Danish paper mill workers
Male
48
1.1 (0.8–1.4)
Female
7
1.0 (0.4–2.1)
Studies Reviewed in Update 1998
Gambini et al., 1997
Italian rice growers
39
0.9 (0.7–1.3)
Kogevinas et al., 1997
IARC cohort
Workers exposed to TCDD (or higher-chlorinated dioxins)
42
0.9 (0.6–1.2)
Workers not exposed to TCDD (or higher-chlorinated dioxins)
30
0.9 (0.6–1.3)
Workers exposed to any phenoxy herbicide or chlorophenol
72
0.9 (0.7–1.1)
Becher et al., 1996
German chemical production workers
Plant I
12
1.3 (0.7–2.2)
Plant II
0
Plant III
0
Plant IV
2
0.6 (0.1–2.3)
Ott and Zober, 1996
BASF cleanup workers
3
1.0 (0.2–2.9)
TCDD <0.1 µg/kg of body wt
0
TCDD 0.1–0.99 µg/kg of body wt
1
1.3 (0.0–7.0)
TCDD >1 µg/kg of body wt
2
1.7 (0.2–6.2)
Ramlow et al., 1996
Pentachlorophenol production workers
0-year latency
4
1.7 (0.4–4.3)
15-year latency
3
1.8 (0.4–5.2)
Studies Reviewed in Update 1996
Blair et al., 1993
US farmers in 23 states
White males
657
1.0 (1.0–1.1)
Nonwhite females
23
1.9 (1.2–2.8)
Bueno de Mesquita et al., 1993
Phenoxy herbicide workers
2
0.7 (01.–2.7)
Collins et al., 1993
Monsanto 2,4-D production workers
0
0 (0.0–1.1)
Kogevinas et al., 1993
IARC cohort—females
NS
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Reference
Study Population
Estimated Casesa
Exposed Relative Risk (95% CI)a
Studies Reviewed in VAO
Ronco et al., 1992
Danish male self-employed farm workers
286
0.9 (*)
Swaen et al., 1992
Dutch herbicide appliers
1
0.5 (0.0–2.7)b
Fingerhut et al., 1991
NIOSH cohort
10
1.0 (0.5–1.9)
Manz et al., 1991
German production workers
12
1.2 (0.6–2.1)
Saracci et al., 1991
IARC cohort
40
0.9 (0.6–1.2)
Wigle et al., 1990
Canadian farmers
246
0.9 (0.8–1.0)
Zober et al., 1990
BASF production workers—basic cohort
3
3.0 (0.8–11.8)
Alavanja et al., 1989
USDA forest or soil conservationists
9
0.7 (0.3–1.3)
Henneberger et al., 1989
Paper and pulp workers
5
1.2 (0.4–2.8)
Solet et al., 1989
Paper and pulp workers
1
0.5 (0.1–3.0)
Alavanja et al., 1988
USDA agricultural extension agents
10
0.7 (0.4–1.4)
Bond et al., 1988
Dow 2,4-D production workers
0
—(0.0–3.7)
Thomas, 1987
Flavor and fragrance chemical production workers
6
1.4 (*)
Coggon et al., 1986
British MCPA production workers
26
0.9 (0.6–1.3)
Robinson et al., 1986
Paper and pulp workers
17
1.2 (0.7–2.1)
Lynge, 1985
Danish male production workers
12
1.3 (*)
Blair et al., 1983
Florida pesticide appliers
4
1.2 (*)
Burmeister et al., 1983
Iowa residents—farming exposures
1,812
1.3 (p < 0.05)
Wiklund, 1983
Swedish agricultural workers
2,599
1.1 (1.0–1.2)c
Burmeister, 1981
Iowa Farmers
338
1.1 (p < 0.01)
Axelson et al., 1980
Swedish railroad workers—total exposure
3
2.2 (*)
ENVIRONMENTAL
New Studies
Fukuda et al., 2003
Residents of municipalities in Japan with or without waste incineration plants in males
Age-adjusted mortality (100,000)
38.2 ± 7.8 vs 39.0 ± 8.8 (p = 0.28)
Age-adjusted mortality (100,000) in females
20.7 ± 5.0 vs 20.7 ± 5.8 (p = 0.92)
Studies Reviewed in Update 2002
Revich et al., 2001
Residents of Chapaevsk, Russia
45.3 in Chapaevsk; 44.0 in Samara Regiond
Age-adjusted incidence (100,000) of stomach cancer in males
Age-adjusted incidence (100,000) of stomach cancer in females
33.9 in Chapaevsk; 17.6 in Samara Regiond
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Reference
Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
Mortality standardized to Samara Region
Males
59
1.7 (1.3–2.2)
Females
45
0.7 (0.5–0.9)
Studies Reviewed in Update 2000
Bertazzi et al., 2001
Seveso residents—20-year follow-up
Zone A males
1
0.5 (0.1–3.2)
Zone A females
2
1.4 (0.3–5.5)
Zone B males
15
1.0 (0.6–1.6)
Zone B females
9
1.0 (0.5–1.9)
Bertazzi et al., 1998
Seveso residents—15-year follow-up
Zone A females
1
0.9 (0.1–6.7)
Zone B males
10
0.8 (0.4–1.5)
Zone B females
7
1.0 (0.5–2.2)
Studies Reviewed in Update 1998
Bertazzi et al., 1997
Seveso residents—15-year follow-up
Zone A females
1
0.9 (0.0–5.3)
Zone B males
10
0.8 (0.4–1.5)
Zone B females
7
1.0 (0.4–2.1)
Zone R males
76
0.9 (0.7–1.1)
Zone R females
58
1.0 (0.8–1.3)
Svensson et al., 1995
Swedish fishermen—mortality
East coast
17
1.4 (0.8–2.2)
West coast
63
0.9 (0.7–1.2)
Swedish fishermen—incidence
East coast
24
1.6 (1.0–2.4)
West coast
71
0.9 (0.7–1.2)
Studies Reviewed in Update 1996
Bertazzi et al., 1993
Seveso residents—10-year follow-up—morbidity
Zone B males
7
1.0 (0.5–2.1)
Zone B females
2
0.6 (0.2–2.5)
Zone R males
45
0.9 (0.7–1.2)
Zone R females
25
1.0 (0.6–1.5)
Studies Reviewed in VAO
Pesatori et al., 1992
Seveso residents
Zones A, B males
7
0.9 (0.4–1.8)
Zones A, B females
3
0.8 (0.3–2.5)
Bertazzi et al., 1989a
Seveso residents—10-year follow-up
Zones A, B, R males
40
0.8 (0.6–1.2)
Zones A, B, R females
22
1.0 (0.6–1.5)
Bertazzi et al., 1989b
Seveso residents—10-year follow-up
Zone B males
7
1.2 (0.6–2.6)
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Reference
Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
VIETNAM VETERANS
New Studies
Akhtar et al., 2004
White Air Force Ranch Hand veterans—cancer of the digestive system
All Ranch Hand veterans
Incidence (SIR)
16
0.6 (0.4–1.0)
Mortality (SMR)
6
0.4 (0.2–0.9)
Veterans, tours 1966–1970—incidence
14
0.6 ((0.4–1.1)
White Air Force comparison veterans—cancer of the digestive system
All comparison veterans
Incidence (SIR)
31
0.9 (0.6–1.2)
Mortality (SMR)
14
0.7 (0.4–1.1)
Veterans, tours 1966–1970—incidence
24
0.9 (0.6–1.3)
Studies Reviewed in Update 1998
Crane et al., 1997a
Australian military Vietnam veterans
32
1.1 (0.7–1.5)
Crane et al., 1997b
Australian national service Vietnam veterans
4
1.7 (0.3–10)
Studies Reviewed in VAO
Breslin et al., 1988
Army Vietnam veterans
88
1.1 (0.9–1.5)
Marine Vietnam veterans
17
0.8 (0.4–1.6)
Anderson et al., 1986a
Wisconsin Vietnam veterans
3
—*
Anderson et al., 1986b
Wisconsin Vietnam veterans
1
—*
a Given when available.
b Risk estimate is for stomach and small intestine.
c 99% CI.
d Incidence rates provided in absence of information on exposed cases or estimated relative risk for morbidity.
* Information not provided by study authors.
—Information denoted by a dash in the original study.
ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; CI, confidence interval; IARC, International Agency for Research on Cancer; MCPA, methyl-4-chlorophenoxyacetic acid; NIOSH, National Institute for Occupational Safety and Health; NS, not significant; USDA, US Department of Agriculture.
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TABLE 6-3 Selected Epidemiologic Studies—Esophageal Cancer
Reference
Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
OCCUPATIONAL
Studies Reviewed in Update 1998
Kogevinas et al., 1997
IARC cohort
Esophagus
28
1.0 (0.7–1.4)
Studies Reviewed in Update 1996
Asp et al., 1994
Finnish herbicide applicators—incidence
3
1.6 (0.3–4.6)
Finnish herbicide applicators—mortality
2
1.3 (0.2–4.7)
Studies Reviewed in VAO
Ronco et al., 1992
Danish male self-employed—incidence farmworkers
32
0.4 (NS)
Saracci et al., 1991
IARC cohort
8
0.6 (0.3–1.2)
Coggon et al., 1986
British MCPA production workers
8
0.9 (0.6–1.3)
Wiklund, 1983
Swedish agricultural workers
169
0.6 (0.5–0.7)
ENVIRONMENTAL
Studies Reviewed in Update 2002
Revich et al., 2001
Residents of Chapaevsk, Russia
Age-adjusted incidence (100,000) in males
4.1 in Chapaevsk; 4.0 in Samara Regionb
Age-adjusted incidence (100,000) in females
0.0 in Chapaevsk; 1.4 in Samara Regionb
VIETNAM VETERANS
Studies Reviewed in Update 1998
Crane et al. 1997a
Australian military Vietnam veterans
Esophagus
23
1.2 (0.7–1.8)
Crane et al. 1997b
Australian national service Vietnam veterans
Esophagus
1
1.3 (0.0–10)
a Given when available.
b Incidence rates provided in absence of information on exposed cases or estimated relative risk for morbidity.
ABBREVIATION: CI, confidence interval; IARC, International Agency for Research on Cancer; ICD-9, International Classification of Diseases, Ninth Edition; MCPA, methyl-4-chlorophenoxyacetic acid; NS, not significant.
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TABLE 6-4 Selected Epidemiologic Studies—Colon Cancer
Reference
Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
OCCUPATIONAL
Studies Reviewed in Update 2000
Steenland et al., 1999
US chemical production workers
34
1.2 (0.8–1.6)
Hooiveld et al., 1998
Dutch chemical production workers
3
1.4 (0.3–4.0)
Rix et al., 1998
Danish paper mill workers
Males
58
1.0 (0.7–1.2)
Females
23
1.1 (0.7–1.7)
Studies Reviewed in Update 1998
Gambini et al., 1997
Italian rice growers
27
1.1 (0.7–1.6)
Kogevinas et al., 1997
IARC cohort
Workers exposed to TCDD (or higher-chlorinated dioxins)
52
1.0 (0.8–1.3)
Workers not exposed to TCDD (or higher-chlorinated dioxins)
33
1.2 (0.8–1.6)
Workers exposed to any phenoxy herbicide or chlorophenol
86
1.1 (0.8–1.3)
Becher et al., 1996
German chemical production workers
Plant I
2
0.4 (0.0–1.4)
Plant II
0
Plant III
1
2.2 (0–12)
Plant IV
0
Ott and Zober, 1996b
BASF cleanup workers
5
1.0 (0.3–2.3)
TCDD <0.1 µg/kg of body wt
2
1.1 (0.1–3.9)
TCDD 0.1–0.99 µg/kg of body wt
2
1.4 (0.2–5.1)
TCDD >1 µg/kg of body wt
1
0.5 (0.0–3.0)
Ramlow et al., 1996
Pentachlorophenol production workers
0-year latency
4
0.8 (0.2–2.1)
15-year latency
4
1.0 (0.3–2.6)
Studies Reviewed in Update 1996
Blair et al., 1993
US farmers in 23 states—white males
2,291
1.0 (0.9–1.0)
Bueno de Mesquita et al., 1993
Phenoxy herbicide workers
3
1.8 (0.4–5.4)
Collins et al., 1993
Monsanto 2,4-D production workers
3
0.5 (0.1–1.3)
Studies Reviewed in VAO
Swaen et al., 1992
Dutch herbicide applicators
4
2.6 (0.7–6.5)
Ronco et al., 1992
Danish male self-employed farm workers
277
0.7 (p < 0.05)
Fingerhut et al., 1991
NIOSH cohort
25
1.2 (0.8–1.8)
Manz et al., 1991
German production workers
8
0.9 (0.4–1.8)
Saracci et al., 1991
IARC cohort
41
1.1 (0.8–1.5)
Zober et al., 1990b
BASF production workers—basic cohort
2
2.5 (0.4–14.1)
Alavanja et al., 1989
USDA forest conservationists
*
1.4 (0.7–2.8)
USDA soil conservationists
*
1.2 (0.7–2.0)
Henneberger et al., 1989
Pulp and paper workers
9
1.0 (0.5–2.0)
Solet et al., 1989
Pulp and paper workers
7
1.5 (0.6–3.0)
Alavanja et al., 1988
USDA agricultural extension agents
*
1.0 (0.7–1.5)
Bond et al., 1988
Dow 2,4-D production workers
4
2.1 (0.6–5.4)
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Reference
Study Population
Exposed Casesa
Estimated Relative Risk (95% CI)a
Thomas, 1987
Flavor and fragrance chemical production workers
4
0.6 (*)
Coggon et al., 1986
British MCPA production workers
19
1.0 (0.6–1.6)
Robinson et al., 1986
Pulp and paper workers
7
0.4 (0.2–0.9)
Lynge, 1985
Male Danish production workers
10
1.0 (*)
Blair et al., 1983
Florida pesticide applicators
5
0.8 (*)
Wiklund, 1983
Swedish agricultural workers
1,332
0.8 (0.7–0.8)c
Thiess et al., 1982
BASF production workers
1
0.4 (*)
Burmeister, 1981
Iowa farmers
1,064
1.0 (NS)
Hardell, 1981
Sweden residents
Exposed to phenoxy acids
11
1.3 (0.6–2.8)
Exposed to chlorophenols
6
1.8 (0.6–5.3)
ENVIRONMENTAL
Studies Reviewed in Update 2002
Revich et al., 2001
Residents of Chapaevsk, Russia
22.7 in Chapaevsk; 21.7 in Samara regiond
Age-adjusted incidence (100,000) in males
Age-adjusted incidence (100,000) in females
13.3 in Chapaevsk; 15.4 in Samara regiond
Mortality standardized to Samara region
Males
17
1.3 (0.8–2.2)
Females
24
1.0 (0.7–1.5)
Studies Reviewed in Update 2000
Bertazzi et al., 2001
Seveso residents—20-year follow-up
Zone A females
2
1.8 (0.4–7.0)
Zone B males
10
1.2 (0.6–2.2)
Zone B females
3
0.4 (0.1–1.3)
Bertazzi et al., 1998
Seveso residents—15-year follow-up
Zone A females
2
2.6 (0.6–10.5)
Zone B males
5
0.8 (0.3–2.0)
Zone B females
3
0.6 (0.2–1.9)
Studies Reviewed in Update 1998
Bertazzi et al., 1997
Seveso residents—15-year follow-up
Zone A females
2
2.6 (0.3–9.4)
Zone B males
5
0.8 (0.3–2.0)
Zone B females
3
0.6 (0.1–1.8)
Zone R males
34
0.8 (0.6–1.1)
Zone R females
33
0.8 (0.6–1.1)
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