Exposure of the American People to Iodine-131 from Nevada Nuclear-Bomb Tests Review of the National Cancer Institute Report and Public Health Implications (1999) / Chapter Skim
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3 Health Risks of I-131 Exposure
3 Health Risks of I-131 Exposure
Pages 45-85
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From page 45... ...
· The relationship of exposure to ionizing radiation and the occurrence of thyroid cancer. · The effect of radiation on the frequency of nonmalignant thyroid disease.
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From page 46... ...
Finally, studies of children whose thyroid glands were exposed to external radiation suggest a strong inverse relationship between age at exposure and the carcinogenic effects of radiation on the thyroid. Over the age of 15, little increase in thyroid cancers has been observed.
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, and differentiated (papillary and follicular) thyroid cancers (Mazzaferri and Jhiang 1994~.
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. The high prevalence of benign thyroid nodules in the general population and among persons with a history of head and neck irradiation increases the risk of false-positive test results.
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From page 49... ...
Those tumors also account for more than 80 percent of the thyroid cancers occurring spontaneously among persons with no known history of thyroid radiation (Mazzaferri 1991~. According to American Cancer Society estimates, 17,200 new cases of thyroid cancer will be diagnosed in 1998 in the United States, ranking thyroid cancer 14th in incidence among 35 categories (Figure 3.2~.
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so oD a a)
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Thus, there is good reason to suspect many healthy people harbor tiny thyroid cancers that will never harm them. The problem of microcancers is not unique to the thyroid gland.
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Thyroid Cancer in Persons (All Ages) Not Exposed to Radiation Most clinically apparent papillary thyroid cancers are first manifested as one or several palpable thyroid nodules, discovered in about half the cases by the patient (Mazzaferri 1993a)
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From page 54... ...
Papillary cancer in children more frequently invades beyond the thyroid capsule, and it metastasizes to regional lymph nodes in almost all cases (Hung 1994; Robbins 1994; De Keyser and Van 1985~. For example, in a study of 98 children with differentiated thyroid cancer (Travagli and others 1995)
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This is the most common event in papillary thyroid cancers occurring naturally (PTC1) and among those in children after the Chernobyl accident (PTC3~.
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In the Japanese atomic bomb study (Thompson and others 1994) , a strong effect of age at exposure on thyroid cancer incidence was seen, such that the excess relative risk (ERR)
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It is the only cohort study of radiogenic thyroid cancer that has included repeated thyroid screening over a period of years. Study limitations include the lack of an unexposed control group with a comparable intensity of screening and uncertainties in the thyroid doses.
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From page 58... ...
of 5 of the major cohort studies of thyroid cancer among those given external radiation at less than 15 years of age. The combined data included 436 thyroid cancers.
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have followed 34,104 patients who were administered I-131 for diagnostic purposes, but only a small TABLE 3.3 Thyroid Cancer Excess Relative Risk (ERR) and Excess Absolute Risk (EAR)
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indicate that 10 clinically significant thyroid carcinomas (plus 7 occult carcinomas) have been detected in this population, in comparison with 2 thyroid cancers found in a group of 227 unexposed persons.
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Weaknesses of the study include its reliance on palpation, the lack of dose information (risk estimates could not be computed) , and the fact that the significant results were appreciably driven by the high nodule rates on the Rongelap and Utirik atolls, where much more thyroid screening occurred (nodules found in the past were included)
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From page 62... ...
Its limitations include the small number of thyroid cancers detected with the consequent low precision of the results. Palpation was used as ultrasonography was not routinely available for screening.
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· Questions about the accuracy of the thyroid dose estimates. · Concerns that thyroid cancer incidence could have been enhanced because some regions were borderline goitrogenic because of low iodine concentrations in drinking water and foods.
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The results of a pooled analysis of 5 epidemiologic studies on infants, children, and adolescents irradiated with externally generated x-rays (Ron and others 1995) , show that there is a steep decline in sensitivity, as measured by ERR, to cancer induction by x-rays with age at exposure.
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From page 65... ...
The authors estimated that, at least in Ukraine, the 95 percent CI around the imputed settlement childhood thyroid doses was about a factor of 2 above and below the estimated doses. The mean settlement doses were then used to derive average thyroid doses for children in various regions, which in turn were regressed on thyroid cancer rates.
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From page 66... ...
. Allowing for the early stage in the expected evolution of solid cancers after exposure to radiation, there is little room for a very markedly reduced efficiency of cancer induction by I-131 compared with that by externally generated x rays.
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From page 67... ...
that have occurred in children exposed to radioactive iodine from the Chernobyl accident are papillary thyroid cancers, but they seem to be more aggressive than usual. However, naturally occurring childhood thyroid cancers are also more aggressive, but not clearly more lethal, than those in adults (Pacini and others 1997; Becker and others 1996; Nikiforov and Gnepp 1994~.
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From page 68... ...
NONMALIGNANT THYROID DISEASE ASSOCIATED WITH RADIOIODINE EXPOSURE Data on the induction of nonmalignant thyroid disease are inconclusive in the I-131 dose range to which most people were exposed from Nevada Test Site fallout. Additional, possibly more conclusive information on the link between low to moderate doses of I-131 and thyroid diseases other than cancer should soon be available from the Hanford Thyroid Disease Study.
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From page 69... ...
High radiation doses clearly can cause direct follicular cell injury, but there 11 is considerable evidence that this is not the only factor involved in radiationrelated nonneoplastic thyroid disease. Various forms of primary thyroiditis are considered to have an autoimmune pathogenesis.
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From page 70... ...
Reports on the populations exposed to radioiodine after the Chernobyl accident are also of interest. Children exposed to I-131 had increased autoantibodies to thyroglobulin, thyroid hormone, and TSH; antithyroid antibodies were increased in a dose-responsive fashion, including apparent increases at doses below 1 Gy (100 red)
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From page 71... ...
Overall, these data clearly indicate that there is a highly significant association between ionizing radiation exposure and the occurrence of nonmalignant thyroid disease at higher levels of exposure. It also is evident that this risk could extend down into the range of doses below 1 Gy (100 red)
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Table 3.4 also gives lifetime thyroid cancer risk for males and females for each age-at-exposure group and total excess cases within each age group. The lifetime risks are obtained by multiplying the SEER 1972-1992 baseline risk estimates (0.25 percent for males,0.64 percent females, which are rates over 85 years for all forms of thyroid cancer including those not linked to radiation exposure)
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From page 73... ...
for the ERR estimate at 1 red and a factor of 2 in the uncertainty of average thyroid dose, gave a range for the total excess cases due to exposure of 11,300-212,000. The central estimate implied (but not explicitly stated in that analysis)
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From page 74... ...
Only one of the studies supports a thyroid cancer effect at dose ranges consistent with average thyroid dose to large birth cohorts from Nevada weapons tests. This study of Israeli children treated with radiation for tinea capitis showed a much stronger dose response than was evidenced in other studies.
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From page 75... ...
Although this chapter has cited histologic evidence suggesting that the differences in thyroid cancers in children exposed from the Chernobyl accident, there are no data yet relevant to effects in adults exposed as children to the I-131 levels associated with the Nevada weapons tests. Given some of the issues noted above, the committee suggests that DHHS consider some additional analyses to evaluate further the estimated confidence intervals for the risk projections and to improve understanding of the sensitivity of the projections to changes in key assumptions.
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For this report, the committee examined thyroid cancer incidence rates by birth cohort using SEER data. It also reviewed an analysis of Idaho registry data and another analysis of SEER data (Gilbert and others, in press for the Journal of the National Cancer Institute)
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The far-western areas were much less exposed to Nevada Test Site fallout than was the rest of the country, so their incidence data are tabulated separately, although considerable migration from eastern to western areas can be assumed to have taken place. For the registries outside the far west, there is some evidence of about a 10 percent excess of thyroid cancers in the exposed birth cohort, but the estimate is not statistically significant.
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From page 78... ...
, which would imply that the power to detect increases in risk should be far greater in the thyroid cancer incidence data than in the mortality data. The impression left by these three studies birth cohort comparisons of incidence in Idaho, birth cohort comparisons in SEER, and the study of Gilbert and colleagues using geographical variation in SEER incidence and thyroid cancer mortality is that there is little evidence of widespread increases in risk related to
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From page 79... ...
Translating the 10 percent increase in risk for these cohorts to excess lifetime risk (using the linear constant excess relative risk model) amounts to approximately 11,300 excess cases (using an RBE of 0.6~.
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From page 80... ...
Males 388,265 59 3.04 Females 407,757 182 8.97 1948-1952 (Monitored in 1988) Males 584,760 102 3.49 14.8 0.4 Females 605,706 294 9.71 8.2 0.4 Estimate of the Number of Cases of Thyroid Cancer That Have Already Been Manifested The population at excess risk of thyroid cancer from I-131 due to fallout from weapons testing at the Nevada Test Site consists of people born between approximately 1940 and 1957.
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From page 81... ...
Because of uncertainty about the doses and the estimates of cancer risk, the number of excess cases of thyroid cancer is impossible to predict except within a wide range. Epidemiological analyses of past thyroid cancer incidence and mortality rates provide little evidence of widespread increases in thyroid cancer risk related to the pattern of exposure to I-131 described in the NCI report.
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From page 82... ...
2For the mathematically inclined reader: The extent of this uncertainty will be a combination of the uncertainty in the dose estimate and the uncertainty in the cancer risk factor derived from epidemiological studies. The uncertainty in the dose estimate will vary with location, with higher uncertainties in those western states nearer to the Nevada Test Site (a factor of 6 to 20 either side of the estimated geometric mean dose)
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Higher Relative Risks result in proportionally higher Percentage Lifetime Risks. 3The thyroid gland would receive on average about 0.001 Sv annually from natural ionizing radiation in the environment.
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This value may be obtained directly from Table 3.4 if certain assumptions can be made. Specifically, the table presents the Percentage Lifetime Risks for individuals who received a radiation dose equal to the average for his or her age cohort as estimated by NCI.
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From page 85... ...
It could be interpreted as the percent chance of developing thyroid cancer during their lifetime to 85+ years of age, or the proportion of 100 people who would develop the disease. For example, if the person was less than 1 year old at time of exposure and his or her individual dose estimate was about 50 red, he or she would calculate a Percentage Lifetime Risk of about 1.1 (males)
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