Mortality from Circulatory Diseases and other Non-Cancer Outcomes among Nuclear Workers in France, the United Kingdom and the United States (INWORKS)

Abstract

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.

An Assessment of Radiation-Associated Risks of Mortality from Circulatory Disease in the Cohorts of Mayak and Sellafield Nuclear Workers

“…The current study adds to the evidence relating to the risk of CD and low-level exposure to radiation, recently reviewed by Azizova, et al (17,23) and Little (16). The pattern of results from studies of CD after low or moderate acute doses and protracted exposures at low dose rates does not point to an obvious explanation, causal or otherwise, for the reported associations (42)(43)(44)(45)(46)(47). Studies of CD in the Japanese atomic bomb survivors have produced results that do not invite a straightforward interpretation because of, inter alia, substantial variation of risks between disease subtypes (42)(43)(44).…”

“…Studies of Russian ''liquidators'' of the Chernobyl accident have reported raised risks of CD incidence with respect to external dose, but based on a surprisingly high proportion of cases among the liquidators (45,46). The authors of the recent INWORKS analysis of CD mortality among nuclear workers (including those from Sellafield), which showed significantly increased ERR/Sv external dose, warned that heterogeneity of risks did not permit firm conclusions to be drawn (47). The findings of the current study reinforce the need for a careful interpretation of a complex set of results, and for future studies to address outstanding issues, such as the influence of major non-radiation risk factors for CD on reported radiation-associated risk estimates.…”

Risk of Leukemia Associated with Protracted Low-Dose Radiation Exposure: Updated Results from the National Registry for Radiation Workers Study

“…Thus, neutron exposure data are likely to be incomplete and some exposure misclassification is unavoidable in this study. Although neutron exposures are likely to be small in relationship to those from photons (42), additional research is needed to understand the effects of neutrons in this study and in other studies of populations exposed to mixed radiation fields.…”

Bilan de la surveillance épidémiologique des travailleurs du cycle électronucléaire en France

“…Au sein d'une cohorte, des analyses de relation dose-risque peuvent être menées pour l'ensemble des causes de décès (Leuraud et al, 2015 ;Richardson et al, 2015 ;Gillies et al, 2017b). Si l'on souhaite approfondir l'étude d'une pathologie en particulier, par exemple le cancer du poumon (Leuraud et al, 2011 ;Grellier et al, 2017) ou les pathologies de l'appareil circulatoire (Drubay et al, 2015), et recueillir des données complémentaires sur les facteurs de risque de cette pathologie comme par exemple, le tabagisme (Leuraud et al, 2011), la glycémie, l'indice de masse corporelle ou l'hypertension (Drubay et al, 2015), la conduite d'une étude cas-témoins nichée dans une cohorte peut constituer une alternative efficiente.…”

“…Cette cohorte a récemment été incluse dans l'étude internationale INWORKS rassemblant plus de 300 000 travailleurs du nucléaire de trois pays (France, Royaume-Uni et États-Unis) (Hamra et al, 2016). L'étude INWORKS a mis en évidence une augmentation du risque de décès associé à la dose cumulée de rayonnements ionisants pour les leucémies (Leuraud et al, 2015), les cancers solides (Richardson et al, 2015) et les maladies de l'appareil circulatoire (Gillies et al, 2017b). Pour les cancers, les coefficients de risque estimés dans INWORKS sont cohérents avec les coefficients de risque dérivés du suivi de la cohorte des survivants des bombardements d'Hiroshima et de Nagasaki, sur lesquels reposent les hypothèses sous-jacentes au système de radioprotection actuellement en vigueur (ICRP, 2007).…”