Comparison of All Solid Cancer Mortality and Incidence Dose-Response in the Life Span Study of Atomic Bomb Survivors, 1958-2009.

Recent analysis of all solid cancer incidence (1958-2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950-2003) was also observed in the 0-2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose-response analyses for all solid cancer mortality and incidence applying similar methods [1958-2009 follow-up, DS02R1 doses, including subjects not-in-city (NIC) at the time of the bombing] and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates throughout Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before January 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose-response exhibited a borderline significant upward curvature among males (P = 0.062) and significant upward curvature among females (P = 0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P = 0.001) but not among females (P = 0.624). The sex difference in magnitude of dose-response curvature was statistically significant for cancer incidence (P = 0.017) but not for cancer mortality (P = 0.781). The results of analyses in the 0-2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose-response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958-1987 vs. 1988-2009) and age at exposure (0-19 vs. 20-83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0-19-year-old male survivors in both calendar periods and among 0-19-year-old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; its evidence appears to depend on the composition of sites comprising all solid cancer group and age at exposure or time. Further follow up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose-response curvature among young survivors and unveil the contributing factors and sites.

THYROID SCREENING AND RELIABILITY OF RADIATION THYROID DOSES FOR THE BELARUSIAN IN UTERO COHORT.

OBJECTIVE: To describe the status and results of thyroid disease screening and assessment of reliability of radiationthyroid doses in the Belarusian in utero cohort of 2,965 individuals exposed to Chernobyl (Chornobyl) fallout. MATERIALS AND METHODS: Thyroid screening examinations are currently underway including thyroid palpation by anendocrinologist, ultrasonographic examination by an ultrasonographer and analysis of blood samples for diagnosisof hypo- and hyperthyroidism, autoimmune thyroiditis, thyroid function tests (thyroid-stimulating hormone [TSH],thyroxine [T4], thyroid peroxidase antibody [anti-TPO], and thyroglobulin antibodies [anti-TG]). Reliability of (i)information from 780 pairs of questionnaires obtained during the first and second interviews of the mothers and (ii)thyroid doses, which were calculated for the cohort members using this information, is evaluated. RESULTS: As of 15 August 2021, 1,267 in utero exposed study subjects had been screened. A single thyroid nodule wasdiagnosed in 167 persons (13.2 % of the total) and multiple thyroid nodules in 101 persons (8.0 %): 189 (14.9 %)persons had nodules detected for the first time at the screening while 79 (6.2 %) persons had nodules detected pre-viously (pre-screening nodules). Fifty-nine out of 268 subjects (22.0 %) with a suspicious thyroid nodule werereferred to fine needle aspiration biopsy, and among them 33 (55.9 %) were biopsied. Reasonable agreement wasobserved for modelqbased doses calculated for the Belarusian in utero cohort members using data from the two inter-views (Spearman's rank-correlation coefficient rs = 0.74, p < 0.001), while measurementqbased doses yielded almost per-fect agreement (rs = 0.99, p < 0.001). CONCLUSIONS: During the thyroid screening, at least one thyroid nodule was identified in 268 of 1,267 (21.2 %) inutero exposed cohort members. Seven thyroid cancer cases were identified in the cohort, including 5 pre-screeningcases and 2 cases detected during the screening. Ongoing research on this unique cohort will provide importantinformation on adverse health effects following prenatal and postnatal exposure to radioiodine and radiocesium iso-topes, for which available epidemiological data are scant.

Breast cancer risk and protracted low-to-moderate dose occupational radiation exposure in the US Radiologic Technologists Cohort, 1983-2008.

BACKGROUND: Although high-dose ionising radiation is associated with increased breast cancer risks, the association with protracted low-dose-rate exposures remains unclear. The US Radiologic Technologist study provides an opportunity to examine the association between low-to-moderate dose radiation and breast cancer incidence and mortality. METHODS: One thousand nine hundred and twenty-two self-reported first primary cancers were diagnosed during 1983-2005 among 66 915 female technologists, and 586 breast cancer deaths occurred during 1983-2008 among 83 538 female cohort members. Occupational breast dose estimates were based on work histories, historical data, and, after the mid-1970s, individual film badge measurements. Excess relative risks were estimated using Poisson regression with birth cohort stratification and adjustment for menopause, reproductive history, and other risk factors. RESULTS: Higher doses were associated with increased breast cancer incidence, with an excess relative risk at 100 mGy of 0.07 (95% confidence interval (CI): -0.005 to 0.19). Associations were strongest for technologists born before 1930 (excess relative risk at 100 mGy=0.16; 95% CI: 0.03-0.39) with similar patterns for mortality among technologists born before 1930. CONCLUSIONS: Occupational radiation to the breast was positively associated with breast cancer risk. The risk was more pronounced for women born before 1930 who began working before 1950 when mean annual doses (37 mGy) were considerably higher than in later years (1.3 mGy). However, because of the uncertainties and possible systematic errors in the occupational dose estimates before 1960, these findings should be treated with caution.

Immune-related conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans.

BACKGROUND: Case-control studies have reported an inverse association between self-reported history of allergy and risk of glioma, but cohort data are limited. Our objectives were to evaluate the associations of major groups of medically diagnosed immune-related conditions (allergy/atopy, autoimmune disease, diabetes, infectious/inflammatory disease) and to explore associations with specific conditions in relation to subsequent diagnosis of brain cancer in a large cohort study. METHODS: We used hospital discharge records for a cohort of 4.5 million male US veterans, of whom 4383 developed primary brain cancer. Rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using time-dependent Poisson regression. RESULTS: We found a significant trend of decreasing RRs for brain cancer with longer duration of allergy/atopy (P=0.02), but not for other conditions studied. Rate ratios of brain cancer for allergy/atopy and diabetes with duration of 10 or more years were 0.60 (95% CI: 0.43, 0.83) and 0.75 (95% CI: 0.62, 0.93), respectively. Several associations with specific conditions were found, but these did not withstand correction for multiple comparisons. CONCLUSIONS: This study lends some support to an inverse association between allergy/atopy and diabetes of long duration and brain cancer risk, but prospective studies with biological samples are needed to uncover the underlying biological mechanisms.