Positive associations between external radiation dose and non-cancer mortality have been found in a number of published studies, primarily of populations exposed to high-dose, high-dose-rate ionizing radiation. The goal of this study was to determine whether external radiation dose was associated with non-cancer mortality in a large pooled cohort of nuclear workers exposed to low-dose radiation accumulated at low dose rates. The cohort comprised 308,297 workers from France, United Kingdom and United States. The average cumulative equivalent dose at a tissue depth of 10 mm [Hp(10)] was 25.2 mSv. In total, 22% of the cohort were deceased by the end of follow-up, with 46,029 deaths attributed to non-cancer outcomes, including 27,848 deaths attributed to circulatory diseases. Poisson regression was used to investigate the relationship between cumulative radiation dose and non-cancer mortality rates. A statistically significant association between radiation dose and all non-cancer causes of death was observed [excess relative risk per sievert (ERR/Sv) = 0.19; 90% CI: 0.07, 0.30]. This was largely driven by the association between radiation dose and mortality due to circulatory diseases (ERR/Sv = 0.22; 90% CI: 0.08, 0.37), with slightly smaller positive, but nonsignificant, point estimates for mortality due to nonmalignant respiratory disease (ERR/Sv = 0.13; 90% CI: −0.17, 0.47) and digestive disease (ERR/Sv = 0.11; 90% CI: −0.36, 0.69). The point estimate for the association between radiation dose and deaths due to external causes of death was nonsignificantly negative (ERR = −0.12; 90% CI: <−0.60, 0.45). Within circulatory disease subtypes, associations with dose were observed for mortality due to cerebrovascular disease (ERR/Sv = 0.50; 90% CI: 0.12, 0.94) and mortality due to ischemic heart disease (ERR/Sv = 0.18; 90% CI: 0.004, 0.36). The estimates of associations between radiation dose and non-cancer mortality are generally consistent with those observed in atomic bomb survivor studies. The findings of this study could be interpreted as providing further evidence that non-cancer disease risks may be increased by external radiation exposure, particularly for ischemic heart disease and cerebrovascular disease. However, heterogeneity in the estimated ERR/Sv was observed, which warrants further investigation. Further follow-up of these cohorts, with the inclusion of internal exposure information and other potential confounders associated with lifestyle factors, may prove informative, as will further work on elucidating the biological mechanisms that might cause these non-cancer effects at low doses.

Twenty-five years have passed since radioactive releases from the Chernobyl nuclear accident led to exposure of millions of people in Europe. Studies of affected populations have provided important new data on the links between radiation and cancer – particularly the risk of thyroid tumours from exposure to iodine isotopes - that are important not only for a fuller scientific understanding of radiation effects, but also for radiation protection. It is now well-documented that children and adolescents exposed to radioiodines from Chernobyl fallout have a sizeable dose-related increase in thyroid cancer, with risk greatest in those youngest at exposure and with a suggestion that deficiency in stable iodine may increase the risk. Data on thyroid cancer risks to other age groups are somewhat less definitive. In addition, there have been reported increases in incidence and mortality from non-thyroid cancers and non-cancer endpoints. Although some studies are difficult to interpret because of methodological limitations, recent investigations of Chernobyl clean-up workers (“liquidators”) have provided evidence of increased risks of leukaemia and other hematological malignancies and of cataracts, and suggestions of an increase in risk of cardiovascular diseases, following low doses and low dose rates of radiation. Further careful follow-up of these populations, including establishment and long-term support of life-span study cohorts, could provide additional important information for the quantification of radiation risks and the protection of persons exposed to low doses of radiation.

PURPOSE: Women who carry germ-line mutations in the BRCA1 and BRCA2 genes are at greatly increased risk of breast cancer (BC). Numerous studies have shown that moderate to high doses of ionizing radiation are a risk factor for breast cancer. Because of the role of the BRCA proteins in DNA repair we hypothesized that BRCA carriers might be more sensitive to ionizing radiation than women in the general population. SUBJECTS AND METHODS: A retrospective cohort study of 1601 female BRCA1/2 carriers was performed.Risk of breast cancer from exposure to chest X-rays as assessed by questionnaire data was analyzed using a weighted Cox proportional hazards model. RESULTS: In this cohort, any reported exposure to chest X-rays was associated with an increased risk of BC (Hazard Ratio (HR)=1.54, P=.007). This risk was increased in carrier women aged 40 and younger (HR=1.97, P<.001), and in women born after 1949 (HR=2.56, P<.001), particularly those exposed only before age 20 (HR=4.64, P<.001 ). CONCLUSION: In our series of BRCA carriers we detected a relatively large effect on BC risk with a level of radiation exposure that is at least an order of magnitude lower than in previously studied medical radiation exposed cohorts. Although part of this increase may be attributable to recall bias, the observed patterns of risk in terms of age at exposure and attained age are consistent with those found in previous studies. If confirmed, the results have important implications for the use of X-ray imaging in young BRCA1/2 carriers. 4