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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2
9
Environmental Radiation Studies
INTRODUCTION
A considerable number of epidemiologic studies have been reported that have attempted to determine whether persons exposed, or potentially exposed, to ionizing radiation from environmental sources are at an increased risk of developing cancer. All epidemiologic studies are inherently uncertain, because they are observational in nature rather than experimental. Nevertheless, not all study designs are equally informative regarding the estimation of radiation risk to humans, and not all epidemiologic studies are of the same quality. Therefore, in evaluating the evidence regarding the risk of exposure to environmental sources of radiation, it is important to consider carefully the specific methodological features of the study designs employed.
Studies of environmental radiation exposure are of three basic designs: (1) descriptive studies, often referred to as ecologic; (2) case-control studies; and (3) cohort or followup studies. The existing published literature consists primarily of reports that are descriptive in nature and ecologic in design. The preponderance of this type of study is due to the fact that they are relatively easy to carry out and are usually based on existing data. Such investigations have utilized incidence, mortality, and prevalence data to estimate disease rates and, typically, to evaluate whether rates of disease vary in a manner that might be related to radiation exposure. If these analyses are based on large numbers of cases or large population groups, such studies may give the appearance of very precise results. Most often, geopolitical boundaries or distance from a source of radiation are used as surrogate means to define radiation exposure. For example, cancer incidence rates might be evaluated as a function of distance from a nuclear facility, or specialized statistical techniques might be employed to determine whether cases of cancer cluster or aggregate in a particular region or time period characterized by potential radiation exposure more than would be expected to occur by chance (i.e., in the absence of any exposure).
Weaknesses associated with studies of this type make them of limited value in assessing risk. The primary limitation is that the unit of analysis is not the individual; thus, generally little or no information is available that is specific to the individual circumstances of the people under study. Of most concern in this regard is the definition of radiation exposure. Ecologic studies generally do not include estimates of individual exposure or radiation dose. Either aggregate population estimates are used to define population dose for groups of people, or surrogate indicators such as distance or geographic location are used to define the likelihood or potential for exposure or, in some cases, an approximate magnitude or level of exposure. This approach has serious limitations. It implies, for example, that residents who live within a fixed distance from a facility are assumed to have received higher radiation doses than those who live at greater distances or than individuals in the larger population as a whole who do not live in the vicinity of the facility. Further, it assumes that everyone within the boundary that defines exposure (or a given level of exposure) is equally exposed or has the same opportunity for exposure. In most situations, such assumptions are unlikely to be accurate, and variability in exposure of individuals within the population may be substantially greater than the exposure attributed on a population basis. The resulting almost certain misclassification of exposure can lead to a substantial overestimation or underestimation of the association of the exposure with the disease under study.
Similarly, there is usually no information available in ecologic studies regarding other factors that might influence the risk of developing the disease(s) under study (i.e., other risk factors). Thus, there is no way to evaluate the impact of such factors in relation to the potential effect of radiation exposure. This inability to evaluate or account for the potential confounding effect of other important factors, or the modifying effect of such factors on risk, makes the ecologic approach of limited use in deriving quantitative estimates of radiation risk.
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A third limitation of the ecologic design is that disease outcome usually is not confirmed at the individual level. Most studies rely on routine reporting, either of mortality through death certificates or of cancer incidence through cancer registration and surveillance systems. Such sources of information vary in their degree of accuracy and completeness, and they can sometimes vary in relation to the surrogate measures being used to define exposure (e.g., geographic area). This can lead to the identification of spurious associations.
Fourth, ecologic studies seldom estimate or account for population migration or movement. This, too, can result in the appearance of spurious associations if aggregate or population measures of radiation exposure actually reflect underlying changes in population mobility with factors such as time, age, or geographic area.
Finally, descriptive studies are often based on a small number of cases of disease. Such studies have low statistical power to detect an association if it truly exists, and they are very sensitive to random fluctuations in the spatial and/or temporal distribution(s) of the disease(s) under study. This is especially true for diseases such as cancer, particularly childhood cancer, which are relatively uncommon on a population basis.
There have also been attempts to evaluate the effect of environmental radiation exposures using the two most common analytical study designs employed in epidemiology: the case-control and the cohort study. Such studies are almost always based on individual-level data and thus are not subject to many of the limitations summarized above for ecologic studies. Nevertheless, each of these study designs is subject to specific weaknesses and limitations. Of most concern in case-control studies is the potential bias that can result in relation to the selection of cases and controls, such that the two groups are differentially representative of the same underlying population. A second important source of bias can be differential recall of information about exposure for cases relative to controls. In cohort studies, a common limitation is the relatively small number of cases for uncommon disease outcomes and the resultant low statistical power. A second concern is the completeness of follow-up of the cohort under study, and equal follow-up and determination of disease status according to exposure. Such limitations of both types of analytic epidemiologic studies may be particularly problematic in investigations of low doses and relatively small increases in disease risk. Under such circumstances, the magnitude of the impact on risk estimates of small or modest biases may be as great or greater than the magnitude of the true disease risk.
In summary, most existing published studies of environmental radiation exposure are ecologic in design. Such studies are limited in their usefulness in defining the risk of disease in relation to radiation exposure or dose. They can sometimes be informative in generating new hypotheses or suggesting directions of study but seldom, if ever, are of value in testing specific hypotheses or providing quantitative estimates of risk in relation to specific sources of environmental radiation. Epidemiologic studies, in general, have limited ability to define the shape of the radiation dose-response curve and to provide quantitative estimates of risk in relation to radiation dose, especially for relatively low doses. To even attempt to do so, a study should (1) be based on accurate, individual dose estimates, preferably to the organ of interest; (2) contain substantial numbers of people in the dose range of interest; (3) have long enough follow-up to include adequate numbers of cases of the disease under study; and (4) have complete and unbiased follow-up. Unfortunately, the published literature on environmental radiation exposures is not characterized by studies with such features.
The accompanying tables provide a summary of the principal studies of environmental radiation exposure published since the BEIR V report (NRC 1990). Articles included in this summary were identified principally from searching the PubMed database of published articles from 1990 through July 2004. Searches were restricted to human studies and were broadly defined: key words included radiation; neoplasms; radiation-induced; radioactive fallout; and environmental radiation. Searches specific to the Chernobyl accident included Chernobyl, Russia, Ukraine, and Belarus as key words. Articles were also identified from UNSCEAR (2000b) and from the usual scientific interactions with other investigators. The tables are organized according to the type of exposure situation under study as follows: (1) populations living around nuclear facilities; (2) populations exposed from atmospheric testing, fallout, or other environmental releases of radiation; (3) populations exposed from the Chernobyl accident; (4) populations exposed from natural background; and (5) children of adults exposed to radiation. Within each type of exposure situation, the tables are further grouped according to study design: ecologic studies, case-control studies, and cohort studies. Each table contains a brief description of the principal design features and results of each study. The principal criteria used to assess the utility of each study in evaluating the risk of disease in relation to radiation exposure were the following: (1) Was there a quantitative estimate of radiation dose; (2) if so, was the estimate for individuals in the study (i.e., individual-level estimates of radiation dose received); and (3) was there a quantitative estimate of disease risk in relation to radiation dose?
POPULATIONS LIVING AROUND NUCLEAR FACILITIES
Table 9-1A lists 16 ecologic studies of populations living around nuclear facilities, 13 of the locations being outside the United States. Most define exposure, or potential for exposure, based on a measure of distance from the facility, although the two studies of exposures at Three Mile Island by Hatch (1992) utilized some information on measurements
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TABLE 9-1A Populations Living Around Nuclear Facilities—Ecologic Studies
Reference
Incidence/Mortality
Population Studied
Type of Exposure
Dates of Accrual
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Hatch and Susser (1990)
Incidence and mortality
Residents (ages 0–24) within 10 miles of Three Mile Island
Background gamma
1975–1985
Outdoor measurements taken in 1976
All cancer; leukemia
49 (0–14)
104 (0–24)
Increased risk for highest vs. lowest quartile; childhood cancer and leukemia
Hatch and others (1990)
Incidence
Residents within 10 miles of Three Mile Island
Xenon and iodine
1975–1985
Dispersion modeling, based on monitoring data
All cancer; childhood cancer (ages 0–14, 0–24); leukemia (ages 0–14, 0–24, 25); and all lymphoma
5493 total
No evidence of an effect on cancer incidence
Jablon and others (1991)
Mortality
Residents of 107 counties in U.S. with or near nuclear installations
Unspecified
1950–1984
County with a nuclear facility that began operation before 1982, or an adjacent county if at least 20% of the county was within a 16 km radius
15 cancer sites; benign and unspecified neoplasms
900,000 deaths in 107 counties
No evidence of excess mortality in study counties
Sofer and others (1991)
Incidence
Children and young adults living near nuclear plant in Israel
Unspecified
1960–1985
Distance from Negev nuclear plant
Leukemia
192
No overall increase; some increase with time among 0–9 in Western Negev; increase in girls 0–4 from 1970 to 1979
Michaelis and others (1992)
Incidence
Children living near nuclear installations in Germany
Unspecified
1980–1990
Distance from nuclear facility
Childhood cancer; acute leukemia
81 within 5 km
No increase for all cancer, acute leukemia; suggested increases in subgroups of early ages or close proximity
McLaughlin and others (1993b)
Incidence and mortality
Children born to mothers residing near nuclear installations in Ontario, Canada
Unspecified
1950–1987
Distance from nuclear facility
Leukemia in children
Range by facility: 2–72
Suggestion of some excess over expected for some analyses; none significant
Bithell and others (1994)
Incidence
Children in England and Wales
Unspecified
1966–1987
Distance from nuclear facilities based on ward
Leukemia and non-Hodgkin’s lymphoma (NHL)
Range for 25 km zones: 7–570
Linear risk score significantly elevated in Sellafield and Burghfield
Black and others (1994a)
Incidence
Residents of Dalgety Bay, Scotland
Particles of radium-226
1975–1990
Routine monitoring measurements
All cancer; 18 specific sites
211 (total)
No evidence of increase over expected
Black and others (1994a)
Incidence
Children and young adults in Dounreay, Scotland
Contamination from nuclear reprocessing plant
1968–1991
Distance from Dounreay
Leukemia and NHL
12 in nearest zone
Evidence of increase over expected in nearest zone
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Reference
Incidence/Mortality
Population Studied
Type of Exposure
Dates of Accrual
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Zaridze and others (1994)
Incidence
Children in Kazakhstan
Unspecified
1981–1990
Distance from nuclear testing sites
All cancer; six specific sites
Total: 1408; leukemia: 512
Increase in leukemia in areas closest to testing sites; some evidence of increase in brain tumors
Viel and others (1995)
Incidence
People under age 25 living around La Hague reprocessing plant in France
Unspecified
1978–1992
Distance from the La Hague plant
Leukemia
25
Cluster of cases located close to La Hague plant
Waller and others (1995)
Incidence
Children in 2594 parishes of Sweden
Unspecified
1980–1990
Distance from nuclear facility
Acute lymphocytic leukemia (ALL)
656
No significant clustering of cases found
Gulis and Fitz (1998)
Incidence
Residents of Trnava, Slovakia
Unspecified
1986–1995
Distance from nuclear power plant
13 cancer sites
Range for zones: 0–323
Suggestion of increasing incidence closer to the site; nonsignificant
Kaatsch and others (1998)
Incidence
Children living near nuclear facilities in Germany
Unspecified
1991–1995
Distance from a nuclear facility
All cancer; leukemia; lymphoma; selected sites
Total 550; leukemia 182
No evidence of an increase in incidence
Guizard and others (2001)
Incidence
Residents under age 25 in areas around the La Hague plant in France
Unspecified
1978–1998
Distance from the La Hague plant
Leukemia
38
Increase over expected in area less than 10 km from site
Boutou and others (2002)
Incidence
Nord Cotentin, France
Population mixing—near nuclear power plant and reprocessing unit
1979–1998
Population mixing index per geographic unit (commune), based on number of workers born outside department of La Manche
Childhood leukemia in persons under age 25
Incidence rate ratio 2.7 in rural communes in highest tertile of mixing, relative to urban communes. Positive trend in leukemia with increasing mixing index. Risk stronger for ALL in children 1–6
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taken around the site after the accident. All but one (Jablon and others 1991) are based on incidence data, and one study in Canada (McLaughlin and others 1993a) uses mortality data as well as incidence data. The focus of most of these investigations is leukemia and/or childhood cancer, although a few include all cancers as an outcome. The size of the studies, in terms of numbers of cases, ranges from very small (Black and others, 1994a; 12 cases in the most highly exposed zone) to extremely large (Jablon and others 1991). Notably, most of the studies do not specify the nature of the radiation exposure, and none of the 16 contains individual estimates of radiation dose. Although some of these studies report an increased occurrence of cancer that could potentially be related to environmental radiation exposures, none provides a direct quantitative estimate of risk in relation to radiation dose.
Table 9-1B summarizes three case-control studies of persons living around a nuclear facility. Two studies are of leu
TABLE 9-1B Populations Living Around Nuclear Facilities—Case-Control Studies
Reference
Population Studied
Number of Subjects
Dates of Accrual
Type of Exposure
Type of Dosimetry
Summary of Results
Cases
Controls
Cases
Controls
Urquhart (1991)
Leukemia and NHL in children under age 15 resident in Caithness
Selected from birth register; matched by zone of residence at birth, date of birth, sex
14
55
Diagnosis 1970–1986
Paternal preconception whole-body dose; antenatal X-ray
Employment at Dounreay; recorded dose from employment records; questionnaire for X-ray
No increased risk with employment at Dounreay, recorded radiation dose, antenatal X-ray; evidence of increased risk from playing on beaches within 50 km of Dounreay
Shields and others (1992)
Congenital and perinatal conditions, stillbirths, infant deaths
Chronologically nearest normal single birth; matched by sex, mother’s age within 5 years, gravidity
266
266
1964–1981
Environmental exposure from working or living near, or working in uranium mines
Environment: time prior to child’s birth worked in uranium mine; residence within 0.5 mile of mine, dumps, or tailings; living in home made with mine rock. Workers: recorded WLM, estimated gonadal dose
Only significant association with mother living near tailings or mine dumps. Overall, associations with measures of radiation exposure were weak
Pobel and Viel (1997)
Leukemia diagnosed in people <25 years of age living within 35 km of La Hague nuclear plant
Sample of children cared for by general practitioners of the cases; matched to cases on sex, age, place of birth; and residence at diagnosis of case
27
192
1978–1993
Antenatal and postnatal X-ray exposure; parental occupational exposures (including radiation); viral infections, life-style
For parents employed in nuclear facility, whole-body external dose (mSv) was obtained from company records. Other information obtained by questionnaire
No association with occupational radiation exposure of parents; increased risk for use of local beaches, consumption of local fish, length of residence in granitic area or house
kemia, one in children under age 15 (Urquhart and others 1991) and the other in people under age 25 (Pobel and Viel 1997). Both studies are based on a small number of cases and focus primarily on parental radiation exposure and X-ray exposure of the child. Neither study found an increased risk associated with these types of radiation exposure. Both, however, did find an increased risk associated with playing on beaches near the nuclear facility. The third study (Shields and others 1992) focuses on congenital and perinatal conditions, stillbirths, and infant deaths in relation to exposures from uranium mines. Exposures include environmental exposures from living near a mine or mine dumps or tailings, or living in a home made from mine rock, as well as from working in a uranium mine. This study does not provide an estimate of radiation risk associated with any of the indicators of exposure.
In summary, most of the studies of populations living around nuclear facilities have not included individual esti-
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Health Risks from Exposure to Low Levels of Ionizing Radiation: Beir VII Phase 2
TABLE 9-2A Populations Exposed from Atmospheric Testing, Fallout, or Other Environmental Release of Radiation—Ecologic Studies
Reference
Incidence/Mortality
Population Studied
Type of Exposure
Dates of Accrual
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Darby and others (1992)
Incidence
Children under age 15 in Nordic countries
Fallout from nuclear weapons tests
Denmark (1948), Finland, Norway, Iceland (1958), Sweden (1961–1987)
Estimates of bone marrow dose to fetus, 1-year-old, testes, received during fallout period: low, medium, high
Leukemia
Not given
Little increase in high-fallout years; slightly elevated in high vs. medium group
Gilbert (1998)
Incidence and mortality
United States
Fallout from nuclear weapons tests in Nevada
Deaths: 1957–1994; incident cases: 1973–1994
Mean thyroid dose by county, derived from measurements and environmental modeling
Thyroid cancer
4602 deaths; 12,657 incident cases
No increased risk with cumulative dose or dose received at ages 1–15; suggested increase for those exposed under age 1 and those in 1950–1959 birth cohort
mates of radiation dose and have therefore not provided an estimate of disease risk. The three case-control studies described above found no increased risk of disease associated with radiation exposure.
POPULATIONS EXPOSED FROM ATMOSPHERIC TESTING, FALLOUT, OR OTHER ENVIRONMENTAL RELEASE OF RADIATION
Table 9-2A describes two ecologic studies of populations exposed to fallout from atmospheric nuclear testing, fallout, or other sources of environmental release of radiation. The nature of the exposure is not specified beyond “fallout.” These studies utilize population-based measures of exposure rather than individual estimates of radiation dose. They address two separate outcomes (leukemia and thyroid cancer), but provide no quantitative estimates of risk associated with the exposure.
Table 9-2B summarizes two cohort studies of persons who participated in U.K. atmospheric nuclear weapons tests. The study by Darby and colleagues (1993) is an extension of an earlier analysis from this cohort and uses doses from film badges to characterize individual external whole-body radiation dose. It investigates all causes of mortality as well as all major forms of cancer. Overall, the study found no increased risk of developing cancer or other fatal diseases as a function of estimated dose received, based on follow-up through 1991 and relatively large numbers of cases. There was some evidence of an increase in leukemia, based on only 29 cases. The most recent update of this cohort (Muirhead and others 2003) found little increase in overall mortality or cancer incidence and no increase in other types of cancer, but continuing evidence of a small increased risk of nonchronic lymphocytic leukemia (CLL).
In contrast, a recent study of U.S. veterans (Dalager and others 2000) who participated in atmospheric nuclear weapons tests reported a significant increase in death from all causes, and for all lymphopoietic cancers combined, although the number of cases in the latter group was very small. This study focused on veterans whose external γ-radiation dose, as recorded on film badges, was 5 rem, and compared mortality in this group to veterans who participated in one nuclear test and whose dose was 0.25 rem. The mean dose among the 5 rem group was 7.8 rem and among the controls was 0.08.
Also included in Table 9-2B are several studies of the population of residents living near the Techa River in the southern Urals of the Russian Federation. More than 25,000 residents were exposed to external γ-radiation as well as internally from fission products (primarily cesium-137, strontium-90, ruthenium-106, and zirconium-95) released into the Techa River from the nearby Mayak plutonium production facility, predominately in the early 1950s. Studies have been conducted of cancer mortality in residents and their offspring, as well as pregnancy outcomes. Initial dose estimates were based on average doses reconstructed for settlements.
Efforts to estimate individual doses for members of this resident cohort continue. To date, there is no evidence of a decrease in birth rate or fertility in the exposed population, and there is no increased incidence of spontaneous abortions or stillbirths (Kossenko and others 1994). There is some evidence of a statistically significant increase in total cancer mortality (Kossenko 1996). Current estimates of the excess absolute risk (EAR)1 of leukemia in this cohort is 0.85 per 10,000 person-years (PY) per gray (95% CI 0.2, 1.5), and for
1
EAR is the rate of disease in an exposed population minus the rate of disease in an unexposed population.
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TABLE 9-2B Populations Exposed from Atmospheric Testing, Fallout, or Other Environmental Release of Radiation—Cohort Studies
Reference
Incidence/Mortality
Cohort Definition
Comparison Group
Dates of Accrual
Type of Exposure
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Darby and others (1993)
Incidence and mortality
Persons who participated in U.K. atmospheric nuclear weapons tests
Men identified from Ministry of Defense archives who did not participate
1950s–1991
External whole-body dose
Recorded on film badges obtained from Ministry of Defense
Broad causes of death; 27 specific cancer sites
All causes: 2753 (control group—2939)
No effect on risk of developing cancer or other fatal diseases; some evidence of an increase over expected for leukemia, based on 29 cases
Kossenko and others (1994)
Pregnancy outcome and mortality
Children born to 28,100 residents exposed to discharges of radioactive waste into Techa River
Unexposed populations living in the same area
1953–1974
External and internal dose: primarily from 137Cs, 90Sr, 106Ru, 95Zr
Gonadal doses estimated as average for each settlement
Birth rate, fertility, fetal loss, infant mortality
56 cancer deaths
No decrease in birth rate or fertility in exposed population; no increased incidence of spontaneous abortions or stillbirths; no change in cancer mortality
Kossenko and others (1994)
Mortality
28,000 residents exposed to discharges of radioactive waste into Techa River, 1950–1953
Unexposed populations living in the same area
1950–1982
External and internal dose: primarily from 137Cs, 90Sr, 106Ru, 95Zr
Average absorbed dose to bone marrow estimated for each settlement
All cancer and 13 major site categories
163 cancers in exposed population
Increase in total cancer mortality. Leukemia: absolute risk 0.85 per 10,000 PY per gray; relative risk for esophagus, stomach, and lung similar to atomic bomb survivors
Kossenko (1996)
Mortality
28,000 residents exposed to discharges of radioactive waste into Techa River
Matched control group from unexposed area
33-year period from 1949 through 1982
External and internal dose: primarily from 137Cs, 90Sr, 106Ru, 95Zr
Average absorbed dose to bone marrow estimated for each settlement
Leukemia and solid cancer in residents; cancer in offspring
Leukemia: absolute risk 0.85 per 10,000 PY per gray; solid cancer: relative risk 0.65 Gy−1. No increase in offspring of exposed residents
Davis and others (2001)
Cumulative incidence
Persons born to mothers resident in one of 7 counties surrounding Hanford Site from 1940 to 1946
Internal control according to estimated individual thyroid radiation dose
Birth through date of exam in 1992–1997
Primarily 131I
Estimated individual absorbed dose to thyroid
Thyroid cancer and 12 categories of noncancer thyroid disease
19 thyroid cancer cases
No increase in thyroid cancer or any noncancer thyroid disease outcome associated with increasing radiation dose to the thyroid
Dalager and others (2000)
Mortality
Persons who participated in U.S. atmospheric nuclear weapons tests and received highest doses
Navy veterans who participated in HARDTACK and received minimal radiation dose
Date of first exposure through 1996
External gamma dose
Film badges
All deaths; lymphopoietic, leukemia, digestive, respiratory, other cancer
300 deaths in veterans with 5 rem; 11 cases of lymphopoietic cancer
All-cause mortality: relative risk (RR) 1.22 (95% CI 1.04–1.44); lymphopoietic cancer 3.72 (95% CI 1.28–10.83)
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Reference
Incidence/Mortality
Cohort Definition
Comparison Group
Dates of Accrual
Type of Exposure
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Kossenko and others (2000)
Mortality
10,459 offspring of parents exposed to discharges of radioactive waste into Techa River
None
1950–1992
External and internal dose: primarily from 137Cs, 90Sr, 106Ru, 95Zr
None
Cancer
25 cancer deaths
Descriptive analyses only—no estimates of risk
Koshurnikova and others (2002)
Mortality and incidence
Ozyorsk Population
72,185 persons living in Ozyorsk for at least 1 year under age 15 and born 1948–1988; or born elsewhere 1934–1988 but moved to Ozyorsk before age 15
1948–1988
Fallout from Mayak facility
None
Deaths, cancer deaths, leukemia, thyroid cancer
4636 deaths; 371 cancer deaths; 53 leukemia deaths; 31 thyroid cancer cases
Thyroid cancer 3–4 times expected relative to Russia; 1.5–2-fold higher based on Chelyabinsk Oblast rates
Muirhead and others (2003)
Mortality and incidence
21,357 persons who participated in the U.K. atmospheric nuclear weapons tests
22,333 men who did not participate in tests identified from Ministry of Defense records, matched on a number of characteristics
1952–1998
External gamma
Film badge readings and potential for exposure based on duties
All deaths, 27 types of cancer
2089 deaths; 785 cancer deaths; 16 leukemia deaths; 2641 cases of cancer; 67 cases of leukemia
Little difference in overall mortality or cancer incidence between exposed and controls; no increase in multiple myeloma; evidence of a small risk of non-CLL leukemia
Takahashi and others (2003)
Prevalence
3709 Marshall Island Residents born before the Castle BRAVO atmospheric nuclear weapons tests on March 1, 1954
Internal control according to estimated dose level
1993–1997
Fallout from Castle BRAVO test
Surrogate estimates of dose based on 137Cs soil deposition levels
Thyroid cancer
57 cases
Prevalence increased with quartile of estimated dose, but was not significant
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solid tumors the relative risk estimate is 0.65 Gy−1 (95% CI −0.3, 1.0). Median dose estimates for soft tissue in this cohort are 7 mSv (maximum 456 mSv) and for bone marrow 253 mSv (maximum 2021 mSv). Estimates of the relative risk for cancer of the esophagus, stomach, and lung are similar to those reported for atomic bomb survivors. There is no evidence of an increase in cancer mortality in the offspring of exposed residents (Kossenko 1996). There has also been one study (Koshurnikova and others 2002) of persons living in the town of Ozyorsk exposed to fallout from the nearby Mayak nuclear facility. This study reported an excess of thyroid cancer three to four times that expected relative to rates for all of Russia and a somewhat lower excess (1.5 to twofold higher) based on a comparison with Chelyabinsk Oblast rates. No estimates of radiation dose were included in this study.
Two other cohort studies of persons exposed to atmospheric releases of radioactive materials are also summarized in Table 9-2B. One is a follow-up study of 3440 persons exposed as young children to atmospheric releases of primarily 131I from the Hanford nuclear facility in eastern Washington State (Davis and others 2001, 2004a). No increased risk of thyroid cancer was found associated with individual radiation dose to the thyroid. The other (Takahashi and others 2003) is a prevalence study of thyroid cancer conducted through screening of 3,709 Marshall Island residents born before the Castle BRAVO atmospheric nuclear weapons test on March 1, 1954. Radiation dose was based on a surrogate constructed from age-specific doses estimated for the Utirik atoll and 137Cs deposition levels on atolls where the participants resided. There was some indication that the prevalence of thyroid cancer increased with quartile of estimated dose, but the increase was not statistically significant.
In summary, some but not all studies of persons exposed to fallout or other environmental releases of radiation have found increased risks of specific disease outcomes. Most notable are findings of a significant increase in death from all causes and for all lymphopoietic cancers combined in a recent study of U.S. veterans who participated in atmospheric nuclear weapons tests, and evidence of an increase in total cancer mortality and thyroid cancer incidence among residents living near the Techa River in the southern Urals of the Russian Federation.
POPULATIONS EXPOSED FROM THE CHERNOBYL ACCIDENT
The explosion at the Chernobyl Power Station Unit 4 in Ukraine on April 26, 1986, released large quantities of radionuclides into the atmosphere, resulting in the contamination of a large geographic area. Initially exposures were due principally to radioisotopes of iodine, primarily iodine-131 (131I), and subsequently to radiocesium, primarily cesium-137 (137Cs), from both external exposure and the consumption of contaminated milk and other foods. Numerous epidemiologic studies have been carried out since the Chernobyl accident to investigate the potential late health consequences of exposure to ionizing radiation from the accident. These studies have focused largely on thyroid cancer in children, but have also included investigations of recovery operation workers and residents of contaminated areas, and have investigated the occurrence of leukemia and solid tumors other than thyroid cancer among exposed individuals.
Overwhelmingly, the published findings are from studies that are ecologic in design and therefore do not provide quantitative estimates of disease risk based on individual exposure circumstances or individual estimates of radiation dose. Most reports are descriptive incidence and prevalence studies that utilize population or aggregate estimates of radiation dose. The principal studies are summarized in Table 9-3A. Only four analytical studies are published that report dose-response results based on individual dose estimates (Table 9-3B). In the sections that follow, current evidence is summarized separately regarding the risk of thyroid cancer, leukemia, and other solid tumors associated with radiation exposure from the Chernobyl accident. Studies of recovery operations workers are considered in Chapter 8 on occupational exposures.
Thyroid Cancer
An increase in the incidence of thyroid cancer first began to appear in Belarus and Ukraine in 1990. After the initial few reports, there was immediate skepticism that such increases were related directly to radiation exposure from Chernobyl. The very early onset of disease after exposure (only 4 years) was unexpected based on existing knowledge of the latent period for radiation-related thyroid cancer; there was doubt about the certainty of the pathologic diagnoses; and there was speculation that the apparent increases were largely the result of widespread population screening.
Numerous reports have continued to describe an increasing number of cases of thyroid cancer, particularly in the most heavily contaminated regions of Ukraine and Belarus, and also in Russia. Collectively, findings reported to date have demonstrated an association between radiation exposure from the Chernobyl accident and an increase in thyroid cancer incidence. Among those under age 18 at the time of the accident, it has been estimated that approximately 2000 thyroid cancers were diagnosed from 1990 to 1998 in Ukraine, Belarus, and Russia. The increase in all three countries for this period was approximately fourfold, with the highest increase observed in the Gomel region in Belarus. More recent data indicate that excess thyroid cancer continues to occur among people in Belarus, Ukraine, and the contaminated regions of Russia. This increase cannot be explained only by the aging of the cohort and the improvement in case detection and reporting. Although there is now little doubt that an excess of thyroid cancer has occurred in highly contaminated areas, there is still very little information re-
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TABLE 9-3A Populations Exposed from the Chernobyl Accident—Ecologic Studies
Reference
Incidence/Mortality
Population Studied
Type of Exposure
Dates of Accrual
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Prisyazhiuk and others (1991)
Incidence
Three contaminated districts in Ukraine: Polesskoye, Naroditchy, Ovrutch
Fallout from Chernobyl
1981–1990
Calendar year (before and after accident) and district (contaminated areas)
Leukemia, thyroid cancer, all other cancer
Leukemia: 105; thyroid: 25; all other: 3804
Overall, incidence rates were not different before and after the accident. Leukemia in age 65+ group increased in 1987 and remained 2–3 times higher; three cases of thyroid cancer diagnosed in 1990 in <14 age group (none 1981–1989); all others increased in 1987 by a third
Ramsay and others (1991)
Incidence
Population of Lothian, Scotland
Fallout from Chernobyl
1978–1989
Calendar year (i.e., from Chernobyl, before and after accident)
Down’s syndrome
Ave.: 12.4 cases per year; range 7 (1989)–26 (1987)
Significant increase in 1986–1987
Baverstock and others (1992)
Incidence
Belarus
Fallout from Chernobyl
1986–1992
Calendar year and region
Thyroid cancer
104
Marked increase beginning in 1990; highest rates in Gomel
Kazakov and others (1992)
Incidence
Six regions of Belarus and Minsk city
Fallout from Chernobyl
1986–1992
Calendar year and region
Thyroid cancer
131
Average of 4 cases per year 1986–1989; 55 in 1991; projected 60 in 1992. Most increase in Gomel
Ivanov and others (1993)
Incidence
Belarus: children ages 0–14
Fallout from Chernobyl
1979–1991
Two time periods: 1979–1985; 1986–1991. Three levels of contamination by region or city
Childhood leukemia
Not given
No change in incidence after Chernobyl accident, and no increase after accident in areas with higher contamination levels
Parkin and others (1993)
Incidence
20 European countries: children ages 0–14
Fallout from Chernobyl
1980–1988
Estimated dose (effective equivalent dose) in 30 countries or regions, obtained from UNSCEAR
Childhood leukemia
3679
Risk of leukemia 1987–1988 relative to before 1986 was not related to radiation exposure
Auvinen and others (1994)
Incidence
Finland: children 0–14 in 1976–1992
Fallout from Chernobyl
1976–1992
Estimated cumulative dose in 2 years after the accident. Based on measurements of dose rate in 455 municipalities. Internal dose estimated from whole-body measurements on sample of 81 children. Municipalities divided into fifths of exposure
Childhood leukemia
Not given
Incidence did not increase in 1976–1992. Relative excess in 1989–1992 was not significantly different from zero
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Hjalmars and others (1994)
Incidence
Sweden: children 0–15
Fallout from Chernobyl
1980–1992
137Cs contamination by geographic area
Childhood acute leukemia
888
No significant increase in childhood acute leukemia in contaminated areas
Petridou and others (1994)
Incidence
Greece: children 0–14
Fallout from Chernobyl
1980–1991
Three time periods: 1980–June 1986; July 1986–June 1988; July 1988–June 1991. Mean fallout levels (based on 137Cs measurements) grouped into 17 geographic regions
Childhood leukemia
968
No evidence of an increased incidence of childhood leukemia in periods after Chernobyl accident. No association between childhood leukemia and region by radiation fallout level
Likhtarev and others (1995)
Incidence
Ukraine: children ages 0–14
Fallout from Chernobyl
1986–1993
Calendar year; 7 geographic zones defined by estimated average thyroid dose to children
Thyroid cancer
418 cases in 0–14 year olds; 248 cases in those 15 and older
Increase beginning in 1989; rate in 1993 was 5 times higher than 1986; higher incidence in zones with higher contamination levels
Prisyazhiuk and others (1995)
Incidence
Four districts in Ukraine: Naroditchy, Ovrutch, Ivankov, Polesskoye
Fallout from Chernobyl
1980–1993
Three time periods: 1980–1985 (before accident); 1986–1993 (after accident); 1980–1993
All cancer; leukemia and lymphoma; thyroid cancer
Not given
Statistically significant increase in thyroid cancer after the accident; no significant increase in all cancer, or leukemia and lymphoma
Stsjazhko and others (1995)
Incidence
Belarus, Russia, Ukraine
Fallout from Chernobyl
1981–1994
Three time periods: 1981–1985 (before accident); 1986–1990; 1991–1994; 6 geographic regions
Thyroid cancer
Since the accident: Belarus, 333; Russia, 23; Ukraine, 209
Increase in thyroid cancer incidence after the accident; most pronounced in most heavily contaminated areas
Sugenoya and others (1995)
Prevalence
Two cities in Belarus (Chechelsk and Bobruisk): children ages 10–15
Fallout from Chernobyl
October 1991–August 1992
Contamination levels (137Cs): Chechelsk 5–>40 Ci/km2; Bobruisk, control area
Thyroid abnormalities
888 screened in Chechelsk; 521 screened in Bobruisk
Significantly higher prevalence of multiple micronodular lesions in diffuse goiter in contaminated city
Gunay and others (1996)
Incidence
Bursa, Turkey: pediatric cases of malignancy
Fallout from Chernobyl
1986–1995
Calendar year, 1986–1995
Acute leukemia, lymphoma, solid tumors
Acute leukemia: 101; lymphoma: 44; solid tumor: 31
Significant increase in acute leukemia after 1986; no significant increase in lymphoma or solid tumor
Ivanov and others (1996)
Incidence
Seven regions of Belarus: children 0–15
Fallout from Chernobyl
1982–1994
Calendar year; 7 geographic regions
Childhood leukemia
Not given
No increase associated with calendar; no difference in rates by geographic region
Kumpusalo and others (1996)
Prevalence
Two villages in Bryansk region of Russia (Mirnyi and Krasnyi): residents ages 3–34
Fallout from Chernobyl
1993
Contaminated area (Mirnyi) and control area (Krasnyi)
Thyroid ultrasound findings
302 screened in Mirnyi; 200 screened in Krasnyi
No pathological U.S. findings in either city. Prevalence of thyroid abnormalities higher in contaminated area: ages 0–9, 8.1% in Mirnyi; 1.6% in Krasnyi
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urothelial biopsies of Ukrainian patients, they concluded that activation of DNA damage repair was detected more frequently among residents of contaminated areas, compared to those of putatively uncontaminated areas (Romanenko and others 2002). Morimura and colleagues (2004) observing p53 gene mutations in 54.5% of 11 and 16.7% of 18 Ukrainian bladder cancers collected before and after the Chernobyl accident, respectively, suggesting the possibility of distinct molecular genetic pathways of bladder cancer induction before and after the accident. Romanenko and colleagues (2000) have also reported that renal carcinoma incidence has increased from 4.7 to 7.5 per 100,000 PY.
In summary, there is now little doubt that an excess of thyroid cancer has occurred in areas highly contaminated by radiation from the Chernobyl accident. Analytical studies further indicate that exposure to radiation from Chernobyl is associated with an increased risk of thyroid cancer and that the relationship is dose dependent. Quantitative estimates of risk from these studies are consistent with estimates from other radiation-exposed populations. There is evidence that young age at exposure and iodine deficiency may be important modifiers of the risk of radiation-induced thyroid cancer. There is no convincing evidence that the incidence of leukemia has increased in children or adult residents of the exposed populations; however, few studies of leukemia have been conducted to date and most have employed ecologic designs that are relatively insensitive. There have been very few studies of the incidence of or mortality from solid cancers other than thyroid cancer in populations exposed to radiation from the Chernobyl accident, and there is no evidence of an increase in any solid cancer type to date.
POPULATIONS EXPOSED FROM NATURAL BACKGROUND
Table 9-4 summarizes four studies of populations exposed from natural background radiation. Two were conducted in China, one in Great Britain, and one in India. A number of different cancer outcomes were studied, based on incidence, mortality, and prevalence data. These studies did not find higher disease rates in geographic areas with high background levels of radiation exposure compared to areas with lower background levels. However, these studies were ecologic in design and utilized population-based measures of exposure rather than individual estimates of radiation dose. Thus, they cannot provide any quantitative estimates of disease risk associated with the exposure levels found in the areas studied.
CHILDREN OF ADULTS EXPOSED TO RADIATION
Table 9-5A lists three ecologic studies of children of adults exposed to radiation. The focus is on preconception parental exposure and the risk of leukemia and lymphoma in
TABLE 9-4 Populations Exposed from Natural Background Radiation—Ecologic Studies
Reference
Incidence/Mortality
Population Studied
Type of Exposure
Dates of Accrual
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Wang and others (1990)
Prevalence
Women ages 50–65 living in Yangjiang, China, vs. nearby control areas
Natural background (mostly external whole-body gamma)
1986 (survey)
Measured external exposure (average annual dose in high-background area: 330 mR; in control area: 114 mR)
Thryoid nodularity, serum thyroid hormone levels, chromosome aberrations
Nodules in high areas (95); in control areas (93)
No difference in prevalence of nodules; no difference in thyroid hormone levels; increased frequency of unstable chromosome aberrations
Lu-xin (1994)
Mortality
Population of Yangjiang, China, vs. control area (not specified)
Natural background radiation
1970–1986
Measured annual external exposure (mR)
11 cancer sites
High-exposure area 914; control 1032
No increase in high-background areas except cervix
Richardson and others (1995)
Incidence
Children under age 15 in Great Britain
Natural background (gamma and radon)
1969–1983
Survey of radon and gamma concentrations in homes; gamma outside; 459 districts
Leukemia
6691
No association of childhood leukemia with indoor or outdoor gamma levels
Nair and others (1999)
Incidence
Population of Karunagappally tuluk in Kerala, India
Thorium deposited along coastal areas (gamma)
1990–1996
Gamma measurements made in each house
All cancers
Not given
No evidence of higher incidence of cancer in areas of
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TABLE 9-5A Children of Adults Exposed to Radiation—Ecologic Studies
Reference
Incidence/Mortality
Population Studied
Type of Exposure
Dates of Accrual
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Kinlen (1993a)
Incidence
Residents of Seascale below age 25 in 1951–1991
Paternal preconception whole-body dose
1951–1991
Lifetime preconception dose obtained from employment records (mSv)
Leukemia and NHL
Leukemia: 5 in Seascale; NHL: 3 in Seascale
Significant excess of leukemia and NHL in Seascale among those born in Seascale, and those born elsewhere
Parker and others (1993)
NA
Children born in Cumbria from 1950 to 1989 to fathers employed at Sellafield
Paternal preconception whole-body dose
NA
Total cumulative and 6-month preconception dose, obtained from employment records
Radiation doses (no diseas
preconception dose is associated with children born in Seascale; mean individual preconception doses consistently lower in Seascale
Wakeford and Parker (1996)
Incidence
Residents of West Cumbria under age 25
Paternal preconception whole-body dose
1968–1985
Cumulative preconception dose obtained from worker records
Leukemia
41
Increased incidence in some groups defined by area and age; no increase associated with paternal preconception dose
the offspring of exposed parents. These studies followed the findings first published by Gardner and colleagues (Gardner and others 1990a, 1990b) suggesting that an excess incidence of leukemia in children in West Cumbria may be due to parental preconception exposure to ionizing radiation during employment at the nearby Sellafield nuclear fuel processing plant. All three studies were conducted in relation to exposures received by parents working at the Sellafield nuclear facility in Great Britain. One study (Parker and others 1993) is a radioecologic study, examining the distribution of possible doses received by fathers employed at Sellafield of children born in Cumbria from 1950 to 1989; it does not address disease outcome. Although there is some evidence of an increased risk associated with measures of individual dose in the other two studies, the findings are based on very small numbers of cases and the results across studies are not consistent.
A larger number of case-control studies have been conducted to investigate the possible relationship between radiation exposure of adults and subsequent cancer in their offspring. Table 9-5B summarizes the results of seven published case-control studies. Six of the seven studies included in the table are investigations that are related to findings first published by Gardner and colleagues (1990b). The six studies summarized here include investigations in England and Wales, Scotland, and Canada. All but one investigated leukemia and/or childhood cancer. The seventh study by Sever and colleagues (1988) is a study of congenital malformations. All but the study by Sorahan and Roberts (1993) used employment records and recorded doses to estimate individual preconception radiation dose. The study by Sorahan and Roberts (1993) used job histories to estimate paternal exposure to ionizing radiation and the potential for exposure to radionuclides in the 6 months prior to the conception of 14,869 children dying of cancer. For all childhood cancers, the RR was 2.9 (95% CI 1.2, 7.1) for those potentially exposed to radionuclides. There was no evidence of an association between external ionizing radiation and cancer risk. The most recent study by Draper and colleagues (1997) found an increased risk of childhood leukemia and NHL among children whose fathers were radiation workers (RR 1.8; 95% CI 1.1, 3.0). The risk was also elevated for all other childhood cancers among offspring of mothers who were radiation workers (RR 5.0; 95% CI 1.4, 26.9). There was no evidence of a dose-response trend. In summary, none of the studies provides quantitative information from dose-response analyses or quantitative estimates of the risk of disease associated with exposure, and results across studies are inconsistent.
Table 9-5C describes cohort studies published regarding the risk of cancer and adverse reproductive outcomes in children of adults exposed to radiation. Two are studies by Gardner and colleagues (1987) that are not based on individual estimates of radiation dose but rather on proximity to the Sellafield nuclear plant at different ages (at birth and while attending school). A third (Roman and others 1999) is an attempt to confirm Gardner’s findings of an increased risk of leukemia and lymphoma in children born to fathers with preconception radiation exposure. Individual paternal preconception exposure was estimated from employment records. Person-years at risk were accrued from date of birth for 39,557 children of male workers and 8883 children of female workers until age 25, cancer diagnosis, or death. A total of 111 cases of malignant cancer were found, but there was no evidence of increased risk relative to the general population. Rate ratios for all cancers (adjusted for calendar
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TABLE 9-5B Children of Adults Exposed to Radiation—Case-Control Studies
Reference
Population Studied
Number of Subjects
Dates of Accrual
Type of Exposure
Type of Dosimetry
Summary of Results
Cases
Controls
Cases
Controls
Sever and others (1988)
Congenital malformations, identified from 3 hospitals in two counties near Hanford
Selected from hospital delivery room records, next live birth, matched by sex, mother’s age (5 years), race
672
977
1957–1980
External whole-body radiation
Recorded doses obtained from Hanford records; estimates in millisieverts
Overall, no association with employment at Hanford; suggestion of increase with parental preconception dose; some increases evident in subgroups
Gardner and others (1990b)
Leukemia and lymphoma in people under 25 born in West Cumbria
From birth register, matched by date of birth and sex: local group, matched by parish; area group, unmatched
Leukemia (52); NHL (22); Hodgkin’s disease (23)
1001
Diagnosis: 1950–1985
Total and 6-month external whole-body preconception exposure; antenatal X-ray
Doses from worker radiation records (British Nuclear Fuels)
Leukemia and NHL higher in children born near Sellafield, and with fathers employed at the plant especially those with high preconception doses
Kinlen (1993b)
Leukemia and lymphoma in people born in Scotland since 1958, diagnosed under age 25
Randomly selected from births, matched by county and sex
1024 leukemia; 237 NHL
3783
1958–1990
Total, 3-month, and 6-month preconception external whole-body dose
Doses from worker records (Scottish nuclear industry)
No significant excess in any subgroup; no association with preconception radiation dose
McLaughlin and others (1993a)
Children in Ontario, 0–14, died from leukemia 1950–1963 or diagnosed 1964–1988, born to mothers living near nuclear facility
Selected from births, matched to case by date of births (3 months) and region of mother’s residence at child’s birth
112
890
Deaths: 1950–1963; diagnosis: 1964–1988
Whole-body external dose, whole-body external tritium dose, radon dose
Recorded doses from National Dose Registry
No increased risk for any exposure period or exposure type
Roman and others (1993)
Leukemia or NHL, diagnosed ages 0–4, born in West Berkshire, Basingstoke, and North Hampshire
Two controls per case selected from birth registers; four per case from delivery registers in study area; matched by sex, date of birth (6 months), area of residence at birth, time of diagnosis
54
324
1972–1989
Exposure to radiation at work
Record of employment in nuclear industry; recorded film badge dose if monitored
Cases were more likely to have a parent employed in the nuclear industry; fathers of cases were more likely to be monitored for radiation; no dose-response evident for fathers monitored
Sorahan and Roberts (1993)
Children dying of cancer under age 16 in England, Wales, and Scotland
Selected from birth register, matched by local authority, sex, date of birth
15,279
15,279
1953–1981
6-month preconception; external whole-body dose; exposure to radionuclides (unsealed sources)
Expert assignment, based on job titles
No association with external exposure; increased risk with potential exposure to radionuclides
Draper and others (1997)
Childhood cancer in Great Britain and Scotland
Selected from birth register for same area, born within 6 months of case, same sex
35,949
38,323
Great Britain: 1952–1986; Scotland: 1987–1990
Total, 3-month and 6-month preconception external whole-body dose
Doses recorded by National Registry for Radiation Workers
Fathers of cases more likely to be radiation workers; no dose-response for any exposure periods for fathers or mothers
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TABLE 9-5C Children of Adults Exposed to Radiation—Cohort Studies
Reference
Incidence/Mortality
Cohort Definition
Comparison Group
Dates of Accrual
Type of Exposure
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Gardner and others (1987)
Mortality
Children attending school in Seascale up to 11/84, born since 1950
U.K. national rates
Beginning school–6/30/86
Presumed exposures from Sellafield
Attending school in community near Sellafield plant
Major categories of causes of death
Total deaths: 10
No increase in relation to national rates for all cancer, all causes, leukemia, or lymphoma
Gardner and others (1987)
Mortality
Children born to mothers resident in Seascale from 1950 to 1983
U.K. national rates
1950–6/30/86
Presumed exposures from Sellafield
Born in community near Sellafield plant
Major categories of causes of death
Total deaths 27; leukemia 5
Approximately tenfold excess of leukemia deaths vs. national rates; 2.5-fold excess for other cancer; no increase for other causes
Black and others (1992)
Incidence
Children born in Dounreay area 1969–1988; children attending local schools in the same period born elsewhere
Scottish national rates by tumor site, sex, age, and calendar year
1969–1988
Presumed exposures from Dounreay nuclear reprocessing plant
Born in or living in Dounreay area of Caithness, Scotland
Leukemia and NHL, Hodgkin’s disease, other cancers
Total cancer cases in birth cohort 5; total cases in school cohort 3
Increased incidence of leukemia in both birth and school cohorts: birth cohort O/E −2.3 (0.7, 5.4); schools cohort O/E −6.7 (1.4, 19.5)
Dickinson and others (1996)
Incidence
260,060 singleton births to mothers resident in Cumbria, U.K.
Children of parents who worked at Sellafield anytime between 1947 and 1989
1950–1989
External dose from ionizing radiation to fathers prior to conception of the child
Recorded radiation dose obtained from Sellafield facility
Sex ratio
Live births to fathers with dose prior to conception: 10,272
Significantly higher sex ratio (1.09; CI 1.06, 1.13) for children of fathers exposed at Sellafield than other Cumbria children. Increased sex ratio (1.4; CI 1.13–1.73) for children of fathers with >10 mSv in 90 d prior to conception
Dummer and others (1998)
Mortality
256,066 live and 4034 stillbirths to mothers resident in Cumbria, U.K.
Observed and expected stillbirth rates by distance (in circles of 5, 10, 15, 20, and 25 km) and direction. Expected estimated from rates in remainder of Cumbria
1950–1989
Presumed exposures from Sellafield
Proximity to and direction from Sellafield of mother’s residence
Stillbirths
Live births to mothers within 25 km of Sellafield: 54,746; stillbirths 888
No evidence that proximity to Sellafield increased risk of stillbirth. No significant increase in stillbirths with distance within any of six directional sectors
Parker and others (1999)
Mortality
248,097 live and 3715 stillbirths to mothers resident in Cumbria, U.K.
Children of father who worked at Sellafield anytime between 1947 and 1989
1950–1989
External and internal dose from ionizing radiation to fathers prior to conception of the child
Recorded radiation dose obtained from Sellafield facility
Stillbirths
Live births in fathers exposed prior to conception: 9078; stillbirths 130
Significant increase in stillbirth with father’s external radiation dose prior to conception: OR per 100 mSV 1.24 (CI 1.04, 1.45). Risk higher for stillbirths with congenital anomaly and highest for neural tube defects
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Reference
Incidence/Mortality
Cohort Definition
Comparison Group
Dates of Accrual
Type of Exposure
Type of Dosimetry
Outcomes Studied
Number of Cases
Summary of Results
Roman and others (1999)
Incidence
Children under age 25 of male employees of three nuclear authorities in Great Britain
External: national rates from England and Wales. Internal: within the cohort by radiation exposure levels
For external analyses: born 1965 or later; for internal, born 1985 or later
External whole-body preconception dose
Employment in nuclear industry; whether monitored for radiation exposure; dose estimates from records
All cancer, leukemia, and NHL
Total cancer 111 leukemia 28
No excess incidence over expected; leukemia in children whose fathers received >100 mSv preconception dose was 5.8 times that in children conceived prior to father’s employment, based on 3 cases; no evidence of any dose-response for leukemia
Doyle and others (2000)
Incidence and mortality
Employees of AWE, AEA and BNF, and for AEA and BNF past employees <75 years old who were included in the pension database
Within the cohort by radiation exposure level
1993–1996
External and internal dose from ionizing radiation to fathers prior to conception of the child
Whether monitored for radiation exposure; if so, dose estimates from records of the nuclear facility
Fetal deaths and congenital malformations
Live births: women 3048; men 20,899 Fetal deaths: women 526; men 2723
Risk of fetal death and congenital malformations not related to whether father was monitored for radiation prior to conception or to the dose of radiation received. Risk of early miscarriage (<13 weeks) was higher if mother was monitored before conception (OR 1.3; CI 1.0, 1.6), but no trend with radiation dose. Risk of stillbirth was also higher (OR 2.2; CI 1.0, 4.6). Risk of any major malformation not associated with maternal monitoring or dose prior to conception
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period, age and sex of child, and the number of children born to each parent) were significantly greater than 1.0 among offspring of fathers who received cumulative external doses of 100 mSv or 10 mSv in the 6 months prior to conception (4.1, 95% CI 1.4, 11.8, 5.1, 95% CI 1.6, 16.9), respectively. It should be noted that these results were based on very few cases (four and three, respectively). No trend of increasing risk with cumulative dose was apparent. None of the three studies provide quantitative estimates of risk based on dose-response analyses, and the results across studies are not consistent. Thus, there is little evidence from epidemiologic studies of a link between parental preconception exposure to ionizing radiation and childhood leukemia or other cancers.
Other possible indices of the occurrence of transmissible genetic damage from preconception exposures include spontaneous abortions, congenital malformations, neonatal mortality, stillbirths, and the sex ratio of offspring. Relatively few epidemiologic studies have been conducted to evaluate these outcomes in relation to preconception radiation exposure. Dickinson and colleagues (1996) examined the sex ratio among children born to fathers employed at Sellafield. Exposure was assessed using two methods: total cumulative radiation dose prior to conception and dose received in the 90 days prior to conception. Total cumulative dose did not account for a significant amount of variation in the sex ratio during the period 1950–1988. No significant trend was observed between sex ratio and exposure 90 d prior to conception, although the sex ratio was increased in children of fathers in the highest-dose category (>10 mSv). Chance could not be ruled out as the reason for this result.
A companion study investigated stillbirths in the offspring of men employed at Sellafield (Parker and others 1999). Individual film badge doses were available by record linkage with the British Nuclear Fuels (BNF) dosimetry database. Significant positive associations between both the total cumulative dose (OR per 100 mSv = 1.24; 95% CI 1.04, 1.45) and the dose during the 90 d prior to conception (OR per 100 mSv = 1.86; 95% CI 1.21, 2.76) and risk of stillbirth were observed.3 A nested case-control study was conducted among radiation workers alone using live births matched on sex and date of birth. In contrast with the cohort analysis, the adjusted OR for exposure 90 d preconception was not significantly different from 1.00 (OR per 100 mSv = 1.08; 95% CI 0.68, 1.74). The total cumulative dose, however, did show a significant association with the occurrence of stillbirth (OR per 100 mSv = 1.24; 95% CI 1.04, 1.45). Although based on only a few exposed individuals, neither analysis indicated the presence of an association with internal exposure to radionuclides. Limitations of the study noted by the authors included the possibility of the existence of residual confounding by year of birth, a time-varying uncertainty (30%) in the recorded film badge doses, and the absence of information on concurrent exposures to organic chemicals in the workplace. An earlier study of stillbirth rates around Sellafield (Dummer and others 1998) found no increase in stillbirths in the resident population within 25 km of the facility.
The Nuclear Industry Family Study in the United Kingdom has also investigated possible links between occupational radiation exposures and reproductive health (Maconochie and others 1999). This study population includes all current employees of the Atomic Energy Authority, Atomic Weapons Establishment, and BNF, as well as past employees who were under age 75 and on record at the pension administration office. Information on reproductive health and health of children was obtained through a mailed questionnaire and linked with data from the employers on occupational exposure to ionizing radiation. The database consists of 53,672 pregnancies, 39,557 reported by men and 8,883 by women. Results of the analysis of fetal deaths and congenital malformations were reported by Doyle and colleagues (2000). The risk of neither fetal death nor major congenital malformation was related to paternal preconception radiation dose. Although early miscarriage was more common among mothers who had been monitored prior to conception (OR 1.3; 95% CI 1.0, 1.6), there was no evidence of a dose-response. Risk of fetal death was higher among mothers who had been monitored prior to conception (OR 2.2; 95% CI 1.0–4.6). ORs were adjusted for parental age, birth order, previous fetal loss, calendar year of the end of pregnancy, and manual versus nonmanual job status. No dose response was evident.
In summary, there have been a number of studies of children of adults exposed to radiation. Ecologic studies are based on very small numbers, and none provide quantitative information from dose-response analyses or quantitative estimates of the risk of disease associated with exposure. There is little conclusive evidence from epidemiologic studies of a link between parental preconception exposure to radiation and childhood leukemia or other cancers. Few studies have been conducted to evaluate other possible indices of the occurrence of transmissible genetic damage from preconception radiation exposures, such as spontaneous abortions, congenital malformations, neonatal mortality, stillbirths, and the sex ratio of offspring. Some but not all studies have found a significant positive association between total cumulative dose, as well as dose during the 90 d prior to conception, and the risk of stillbirth. The risk of neither fetal death nor major congenital malformation has been related to paternal preconception radiation dose.
EXPOSURE TO RADIOACTIVE IODINE 131
In evaluating the evidence regarding the risk of cancer associated with exposure to environmental sources of radia-
3
OR represents the odds of being exposed among diseased persons divided by the odds of being exposed among nondiseased persons.
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tion, internal exposure to 131I is of particular concern regarding the risk of thyroid cancer. In contrast to the considerable amount of information that is available from numerous studies of external radiation exposure, there is relatively little information regarding the risk of thyroid cancer in humans exposed to 131I. Existing evidence comes from studies of 131I administered for therapeutic or diagnostic purposes and from various environmental exposure settings, most notably from recent studies of persons exposed to radiation from the Chernobyl accident (reviewed above).
Studies of therapeutic and diagnostic 131I exposures are described in detail in Chapter 7. In brief, early studies of persons receiving therapeutic 131I for hyperthyroidism found no convincing evidence that the risk of thyroid cancer was increased (Dobyns and others 1974; Safa and others 1975; Holm and others 1980a; Holm 1984); most of the participants were adults at the time of exposure, were followed for very short periods, had existing thyroid disease at the time of treatment, and were treated with radiation doses that were quite high (generally 20,000–100,000 mGy). Results from a follow-up (Ron and others 1998a) of one of these studies (Dobyns and others 1974) suggest an increased risk of death from thyroid cancer in patients previously treated with 131I, but the numbers of excess deaths were small and it is likely that underlying thyroid disease might have contributed to these results. Similar results were obtained from a study of 7400 patients who were treated with radioiodine from 1950 to 1991 in England (Franklyn and others 1999). Studies have also evaluated persons exposed to much lower doses (generally 500–1000 mGy) through diagnostic procedures (Holm and others 1980a, 1980b; Hall and others 1996). Although there is some evidence of a small increase in thyroid cancer associated with such exposures, there is a lack of consistency and the small increases in thyroid cancer in some studies are likely due to the underlying thyroid condition. As for the therapeutic studies described above, these too are primarily of persons exposed as adults. The thyroid gland is more radiosensitive in children than adults, most likely because of more rapid growth in infants and children (Williams 2003) and because of differences in metabolism (Mettler and others 1996).
Only a few studies have evaluated the effects of environmental exposure to radioactive iodine. In contrast to the medical exposures summarized above, which were due exclusively to 131I, environmental exposures have generally contained mixtures of 131I, external radiation, and short-lived radioiodines. Initial studies of thyroid disease incidence in Utah schoolchildren exposed to fallout from atmospheric nuclear weapons testing at the Nevada Test Site appeared to show no difference in thyroid disease outcomes compared to children from unexposed areas (Rallison and others 1975). However, a follow-up study reported a slight excess risk of thyroid neoplasms associated with radioiodine exposure (Kerber and others 1993). Although positive dose-response trends were also noted for total nodules and thyroid cancer (when analyzed separately), they were not statistically significant. The study was limited by small numbers of exposed individuals and a low incidence of thyroid neoplasms and by the fact that the examiners were not blinded to exposure. In contrast, a follow-up study of 3440 persons exposed as young children to atmospheric releases of primarily 131I from the Hanford Site found no increased risk of thyroid cancer associated with individual radiation dose to the thyroid (Davis and others 2001, 2004a).
The explanation for the apparent difference in results in the Utah study and the Hanford study is not clear. One possibility is that the exposures were substantially different in terms of the mix of radionuclides and the dose rate. Thyroid dose at Hanford was due almost entirely to 131I, whereas in Utah there was greater contribution from other radioiodines as well as external sources. Exposures in Utah were also more concentrated and episodic than at Hanford, corresponding to specific nuclear tests. This likely resulted in doses being delivered at substantially higher dose rates (although the total dose among 3545 study participants for whom thyroid doses could be estimated [mean 98 mGy] was similar to Hanford doses). A second possibility is that the Utah study’s estimated dose-response could have been biased in the direction of finding an association because the collection of dietary consumption data took place after thyroid disease classification was known for each participant.
Extensive evaluation of the population of the Marshall Islands has shown an increase in benign and malignant thyroid nodules in residents of the northern atolls of Rongelap and Utirik (Conard 1980, 1984). In addition, a retrospective cohort study of more than 7000 Marshall Islanders showed that the prevalence of palpable thyroid nodularity ( 1.0 cm) decreased linearly with increased distance from the Bikini test site (Hamilton and others, 1987). More recently, there has been extensive investigation of populations exposed to radioactive fallout (including 131I as a substantial component) after the Chernobyl accident. Findings from these studies are reviewed and summarized above.
In summary, studies of exposure to 131I from therapeutic and diagnostic uses provide some evidence of a small increase in thyroid cancer associated with such exposures, but there is lack of consistency in the findings. Furthermore, the small increases in thyroid cancer observed in some studies are likely due to the underlying thyroid condition, not to radiation exposure. Results from environmental exposures have been inconsistent. Findings of an increase in thyroid neoplasia in persons exposed to fallout in the Marshall Islands are limited by the lack of individual dosimetry. No excess risk of thyroid cancer was found in residents exposed to radiation from Hanford, and the slight excess risk of thyroid neoplasms associated with radioiodine exposure of Utah residents from the Nevada Test Site was based on small numbers.
In contrast, substantial increases in thyroid cancer have been reported in areas contaminated with radioactive fallout
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from Chernobyl, primarily among children. Although much of the thyroid dose from Chernobyl is due to 131I, exposure to a mix of other radionuclides and the lack of individual dose estimates in most of the studies to date have made it difficult to develop quantitative risk estimates for radiation dose from 131I. However, there is now emerging evidence indicating that exposure to radiation from Chernobyl is associated with an increased risk of thyroid cancer and that the relationship is dose dependent. These findings are based on individual estimates of thyroid radiation dose and reveal strong and statistically significant dose-related increased risks that are consistent across studies. Thus, although the precise quantitative relationship between radiation dose from 131I and the development of thyroid neoplasia remains uncertain at this time, recent findings from studies around Chernobyl and Hanford provide important quantitative estimates of risk as a function of dose.
DISCUSSION
A considerable number of papers have been published from studies that have attempted to determine whether persons exposed, or potentially exposed, to ionizing radiation from environmental sources are at an increased risk of developing cancer. The existing published literature consists primarily of reports that are descriptive in nature and ecologic in design. Such studies are limited in their usefulness in defining risk of disease in relation to radiation exposure or dose. They can sometimes be informative in generating new hypotheses or suggesting directions for study, but seldom, if ever, are they of value in testing specific hypotheses or providing quantitative estimates of risk in relation to specific sources of environmental radiation. Fewer attempts have been made to evaluate the effect of environmental radiation exposures using the two most common analytical study designs employed in epidemiology: the case-control study and the cohort study. Such studies are almost always based on individual-level data and thus are not subject to many of the limitations inherent in ecologic studies. They can potentially provide quantitative estimates of risk based on individual radiation dose.
Epidemiologic studies, in general, have limited ability to define the shape of the radiation dose-response curve and to provide quantitative estimates of risk in relation to radiation dose, especially for relatively low doses. To be informative in this regard a study should (1) be based on accurate, individual dose estimates, preferably to the organ of interest; (2) contain substantial numbers of people in the dose range of interest; (3) have long enough follow-up to include adequate numbers of cases of the disease under study; and (4) have complete and unbiased follow-up. Unfortunately, the published literature on environmental radiation exposures is not characterized by studies with such features.
Sixteen ecologic studies of populations living around nuclear facilities are summarized, thirteen of the locations being outside the United States. Most define exposure, or potential for exposure, based on a measure of distance from the facility, and the focus of most of these investigations is leukemia and/or childhood cancer, although a few include all cancers as an outcome. Notably, most of the studies do not specify the nature of the radiation exposure, and none of the 16 contain individual estimates of radiation dose. Although some of these studies report an increased occurrence of cancer that could be related potentially to environmental radiation exposures, none provide a direct quantitative estimate of risk in relation to radiation dose. There have been three case-control studies of persons living around a nuclear facility. One focuses on congenital and perinatal conditions, stillbirths, and infant deaths in relation to exposure from uranium mines. This study does not provide an estimate of radiation risk associated with any of the indicators of exposure. The other two are of leukemia in children and young adults. Neither study found an increased risk associated with parental radiation exposure and X-ray exposure of the child, but both did find an increased risk associated with playing on beaches near the nuclear facility.
Several cohort studies have been reported of persons exposed to environmental radiation under various circumstances: participation in atmospheric nuclear weapons tests conducted by the United Kingdom and the United States; residents and their offspring living near the Techa River in the southern Urals of the Russian Federation and exposed from the nearby Mayak nuclear complex; residents living near the Hanford Site in eastern Washington State; and residents of the Marshall Islands. Overall, studies of persons who participated in U.K. atmospheric nuclear weapons tests found no increased risk of developing cancer or other fatal diseases as a function of estimated dose received, but there was some evidence of an increase in non-CLL leukemia. In contrast, a recent study of U.S. veterans who participated in atmospheric nuclear weapons tests reported a significant increase in death from all causes and for all lymphopoietic cancers combined.
Results from studies of residents living near the Techa River have found no evidence of a decrease in birth rate or fertility in the exposed population and no increased incidence of spontaneous abortions or stillbirths. There is some evidence of a statistically significant increase in total cancer mortality. Estimates of the relative risk for cancer of the esophagus, stomach, and lung are similar to those reported for atomic bomb survivors. There is no evidence of an increase in cancer mortality in the offspring of exposed residents. The one study of persons living in the town of Ozyorsk exposed to fallout from the nearby Mayak nuclear facility reported an excess of thyroid cancer three to four times that expected relative to rates for all of Russia and a somewhat lower excess (1.5 to twofold higher) based on a comparison with Chelyabinsk Oblast rates.
A follow-up study of persons exposed as young children to atmospheric releases primarily of 131I from the Hanford
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Site in eastern Washington State found no increased risk of thyroid cancer associated with individual radiation dose to the thyroid. A prevalence study of thyroid cancer conducted through screening of 3709 Marshall Island residents born before the Castle BRAVO atmospheric nuclear weapons test on March 1, 1954, found some indication that the prevalence of thyroid cancer increased with quartile of estimated dose, but the increase was not statistically significant.
Numerous epidemiologic studies have been carried out since the Chernobyl accident to investigate the potential late health consequences of exposure to ionizing radiation from the accident. These studies have focused largely on thyroid cancer in children, but have also included investigations of recovery operation workers and residents of contaminated areas, and have investigated the occurrence of leukemia and solid tumors other than thyroid cancer among exposed individuals. Overwhelmingly, the published findings are from studies that are ecologic in design and therefore do not provide quantitative estimates of disease risk based on individual exposure circumstances or individual estimates of radiation dose. Most reports are descriptive incidence and prevalence studies that utilize population or aggregate estimates of radiation dose. Only three analytical studies are published that report dose-response results based on individual dose estimates.
Numerous reports have continued to describe an increasing number of cases of thyroid cancer, particularly in the most heavily contaminated regions of Ukraine and Belarus, as well as in Russia. Collectively, findings reported to date have demonstrated an association between an increase in thyroid cancer incidence and radiation exposure from the Chernobyl accident. This increase cannot be explained only by the aging of the cohort and the improvement of case detection and reporting. Although there is now little doubt that an excess of thyroid cancer has occurred in highly contaminated areas, there is still very little information regarding the quantitative relationship between radiation dose to the thyroid from Chernobyl and the risk of thyroid cancer. Results from three analytical studies published indicate that exposure to radiation from Chernobyl is associated with an increased risk of thyroid cancer and that the relationship is dose dependent. The findings from these studies are consistent with descriptive reports from contaminated areas of Ukraine and Belarus, and the quantitative estimate of thyroid cancer risk is generally consistent with estimates from other radiation-exposed populations. Available data on exposure from the Chernobyl accident are largely in agreement with observations from other studies showing that exposure at the youngest ages is associated with the greatest risk of thyroid cancer. At present no data are available from Chernobyl regarding the risk of thyroid cancer from in utero exposure. Fifteen years after the Chernobyl accident, thyroid cancer incidence is still highly elevated. An increase in thyroid cancer has been observed in both males and females, and most of the Chernobyl studies have reported similar relative risks per unit dose for males and females. Iodine deficiency also appears to be an important modifier of the risk of radiation-induced thyroid cancer, and there is some evidence that iodine deficiency enhances the risk of thyroid cancer following radiation exposure. Finally, relatively little has been published regarding thyroid outcomes other than thyroid cancer, although one study has reported an elevated risk of benign thyroid tumors and there have been reports of increases in autoimmune disease and antithyroid antibodies following childhood exposure to Chernobyl.
Evidence from epidemiologic studies regarding the risk of leukemia in the general population reflects low-dose-rate exposure (primarily from 137Cs), which has occurred for a number of years and will continue to occur in the future. These resident populations were exposed at all ages, but studies of residents are primarily of persons exposed as children and/or in utero.
At present, the available evidence from ecologic studies does not convincingly indicate an increased risk of leukemia among persons exposed in utero to radiation from Chernobyl. There are no data from analytic epidemiologic studies in which individual dose estimates are available. The existing evidence does not support the conclusion that the rates of childhood leukemia have increased as a result of radiation exposure from the Chernobyl accident. However, ecologic studies of the types conducted to date are not particularly sensitive to detecting relatively small changes in the incidence of a disease as uncommon as childhood leukemia over time or by different geographic areas. The single analytical study is insufficient to draw conclusions regarding leukemia risk after exposure of children to Chernobyl. There is also no convincing evidence that the incidence of leukemia has increased in adult residents of the exposed populations that have been studied in Russia and Ukraine. However, few studies of the general adult population have been conducted, and they have employed ecologic designs that are relatively insensitive.
There has been relatively little study of the incidence or mortality from solid cancers other than thyroid cancer in populations exposed to radiation from the Chernobyl accident. Two studies have investigated solid cancer incidence in liquidation workers. They reported increases of cancer incidence during the periods, but generally the excesses were relatively small and not statistically significant. No descriptive or analytical epidemiologic studies of breast cancer risk in populations exposed to radiation from Chernobyl have been published in the peer-reviewed literature; however, one monograph has cited elevated breast cancer incidence rates based on Ukrainian registries. Similarly, although no descriptive or analytical epidemiologic studies of bladder or kidney cancer risk in relation to Chernobyl have been published in the peer-reviewed literature, there has been a series of papers investigating aspects of possible radiation carcinogenesis in these organs.
Four ecologic studies of populations exposed to natural background radiation have been reported. Two were con-
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ducted in China, one in Great Britain, and one in India. These studies did not find any association between disease rates and indicators of high background levels of radiation, and they do not provide any quantitative estimates of disease risk.
Three ecologic studies of children of adults exposed to radiation have been published, with a focus on preconception parental exposure and the risk of leukemia and lymphoma in the offspring of exposed parents. All three studies were conducted in relation to exposures received by parents working at the Sellafield nuclear facility in Great Britain. Although there is some evidence of an increased risk associated with measures of individual dose, the findings are based on very small numbers of cases and the results across studies are not consistent. A larger number of case-control studies have been conducted to investigate the possible relationship between radiation exposure of adults and subsequent cancer in their offspring. In summary, none of the studies provide quantitative information from dose-response analyses or quantitative estimates of the risk of disease associated with exposure, and results across studies are inconsistent. There have been three cohort studies published regarding the risk of cancer in children of adults exposed to radiation. None of the three provide quantitative estimates of risk based on dose-response analyses, and the results across studies are not consistent. Thus, there is little conclusive evidence from epidemiologic studies of a link between parental preconception exposure to ionizing radiation and childhood leukemia or other cancers.
Other possible indices of the occurrence of transmissible genetic damage from preconception exposures include spontaneous abortions, congenital malformations, neonatal mortality, stillbirths, and the sex ratio of offspring. Relatively few epidemiologic studies have been conducted to evaluate these outcomes in relation to preconception radiation exposure, and there is no consistent evidence of an association of any such outcomes with exposure to environmental sources of radiation.
Studies of exposure to 131I from therapeutic and diagnostic uses provide some evidence of a small increase in thyroid cancer, but the small increase observed is likely due to the underlying thyroid condition, not to radiation exposure. Findings of an increase in thyroid neoplasia in persons exposed to fallout in the Marshall Islands are limited by the lack of individual dosimetry. No excess risk of thyroid cancer was found in residents exposed to radiation from Hanford, and only a slight excess risk of thyroid neoplasms was found associated with radioiodine exposure of Utah residents from the Nevada Test Site. In contrast, substantial increases in thyroid cancer have been reported in areas contaminated with radioactive fallout from Chernobyl, primarily among children. Recent evidence from three population-based case-control studies indicates that exposure to radiation from Chernobyl is associated with an increased risk of thyroid cancer and that the relationship is dose dependent. These findings are based on individual estimates of thyroid radiation dose and reveal strong and statistically significant dose-related increased risks that are consistent across studies. They provide important quantitative estimates of risk as a function of dose, primarily from 131I.
SUMMARY
This chapter reviews the evidence from peer-reviewed articles published since BEIR V (NRC 1990) of the relationship between exposure to ionizing radiation from environmental sources and human health.
Ecologic studies of populations living around nuclear facilities neither contain individual estimates of radiation dose nor provide a direct quantitative estimate of risk in relation to radiation dose. Similarly, the one case-control study of congenital and perinatal conditions, stillbirths, and infant deaths in relation to exposures from uranium mines does not provide an estimate of the risk associated with any of the indicators of exposure, and two ecologic studies of populations exposed to fallout from atmospheric nuclear testing or other sources of environmental release of radiation provide no quantitative estimates of the risk associated with presumed exposure.
Several cohort studies have been reported of persons exposed to environmental radiation under various circumstances. No increased risk of developing cancer or other fatal diseases was found in persons who participated in U.K. atmospheric nuclear weapons tests, but there was some evidence of an increase in non-CLL leukemia. U.S. veterans who participated in atmospheric nuclear weapons tests reported a significant increase of death from all causes and for all lymphopoietic cancers combined. There is no evidence of a decrease in birth rate or fertility or an increased incidence of spontaneous abortions or stillbirths in residents living near the Techa River in the Russian Federation. There is some evidence of a statistically significant increase in total cancer mortality, but no evidence of an increase in cancer mortality in the offspring of exposed residents. Persons living in the town of Ozyorsk (Russia) exposed to fallout from the nearby Mayak nuclear facility reported an excess of thyroid cancer (1.5–4 times higher than expected). No increased risk of thyroid cancer was found associated with individual radiation dose to the thyroid in persons exposed as young children to atmospheric releases primarily of 131I from the Hanford Site in eastern Washington State. There is some indication that the prevalence of thyroid cancer among Marshall Island residents born before the Castle BRAVO atmospheric nuclear weapons test increased with quartile of estimated dose, but the increase was not statistically significant.
There continues to be an increasing number of cases of thyroid cancer in populations exposed to radiation from the Chernobyl accident that cannot be explained only by the aging of the cohort and the improvement in case detection and reporting. Results from three analytical studies indicate that exposure to radiation from Chernobyl is strongly associated
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with an increased risk of thyroid cancer in a dose-dependent manner, and the quantitative estimate of thyroid cancer risk generally is consistent with estimates from other radiation-exposed populations and is observed in both males and females. At present, no data are available from Chernobyl regarding the risk of thyroid cancer from in utero exposure. Iodine deficiency appears to be an important modifier of risk, enhancing the risk of thyroid cancer following radiation exposure from Chernobyl. Relatively little has been published regarding thyroid outcomes other than thyroid cancer, although one study has reported an elevated risk of benign thyroid tumors and there have been reports of increases in autoimmune disease and antithyroid antibodies following childhood exposure to Chernobyl.
Evidence from ecologic studies does not indicate an increased risk of leukemia among persons exposed in utero to radiation from Chernobyl nor that rates of childhood leukemia have increased. A single analytical study is insufficient to draw conclusions regarding leukemia risk after exposure of children to Chernobyl. There is no convincing evidence that the incidence of leukemia has increased in adult residents of the exposed populations that have been studied in Russia and Ukraine. There has been very little study of the incidence or mortality from solid cancers other than thyroid cancer in populations exposed to radiation from the Chernobyl accident, and there is no evidence of significant excesses of any other solid cancer type.
Four ecologic studies of populations exposed from natural background radiation did not find any association between disease rates and indicators of high background levels of radiation exposure (for a general discussion of the limitations of ecologic studies see the introduction to this chapter and, more specifically in reference to studies of populations exposed from natural background radiation, see Appendix D, “Hormesis and Epidemiology”).
Ecologic studies of children of adults exposed to radiation while working at the Sellafield nuclear facility in Great Britain have suggested some increased risk of leukemia and lymphoma associated with individual dose, but the findings are based on very small numbers of cases and the results across studies are not consistent. A larger number of case-control studies provides no quantitative estimates of the risk of disease in offspring of exposed parents, and results across studies are inconsistent. None of three published cohort studies provide quantitative estimates of risk based on dose-response analyses, and the results across studies are not consistent. Relatively few epidemiologic studies have been conducted to evaluate outcomes such as spontaneous abortions, congenital malformations, neonatal mortality, stillbirths, and the sex ratio in relation to preconception radiation exposure, and there is no consistent evidence of an association of any such outcomes with exposure to environmental sources of radiation.
In contrast to the considerable amount of information that is available from numerous studies of external radiation exposure, there is relatively little information regarding the risk of thyroid cancer in humans exposed internally to 131I. There is some evidence of a small increase in thyroid cancer associated with exposure to 131I from therapeutic and diagnostic uses, but the findings are inconsistent and the small increases in thyroid cancer observed in some studies are likely due to the underlying thyroid condition, not to radiation exposure. Results from environmental exposures have also been inconsistent. An increase in thyroid neoplasia has been observed in persons exposed to fallout in the Marshall Islands, but no excess risk of thyroid cancer was found in residents exposed to radiation from Hanford, and the slight excess risk of thyroid neoplasms associated with radioiodine exposure in Utah residents from the Nevada Test Site was based on very small numbers. In contrast, substantial increases in thyroid cancer have been reported in areas contaminated with radioactive fallout from Chernobyl, primarily among children. Recent evidence indicates that exposure to radiation from Chernobyl is associated with an increased risk of thyroid cancer and that the relationship is dose dependent. These findings are based on individual estimates of thyroid radiation dose and reveal strong and statistically significant dose-related increased risks that are consistent across studies.
Representative terms from entire chapter:
radiation exposure
