Ischemic Heart Disease Mortality and Occupational Radiation Exposure in a Nested Matched Case-Control Study of British Nuclear Fuel Cycle Workers: Investigation of Confounding by Lifestyle, Physiological Traits and Occupational Exposures.

Epidemiological studies have suggested a link between low-level radiation exposure and an increased risk of cardiovascular disease, but the possibility of bias or confounding must be considered. We analyzed data from a matched case-control study nested in a cohort of British male industrial (i.e., blue-collar) nuclear fuel cycle workers using paired conditional logistic regression. The cases were comprised of workers from two nuclear sites who had died from ischemic heart disease (IHD) and were matched to controls on nuclear site, date of birth and first year of employment (1,220 pairs). Radiation doses from external sources and to the liver from internally deposited plutonium and uranium were obtained. Models were adjusted for age at start of employment at either site, decade of start, age at exit from study (death or censoring), process/other worker and socio-economic status. Included potential confounding factors of interest were occupational noise, shift work, pre-employment blood pressure, body mass index and tobacco smoking. Cumulative external doses ranged from 0-1,656 mSv and cumulative internal doses for those monitored for radioactive intakes ranged from 0.004-5,732 mSv. In a categorical analysis, additionally adjusted for whether or not a worker was monitored for internal exposure, IHD mortality risk was associated with cumulative external unlagged dose with a 42% excess risk (95% CI: 4%, 95%) at >103 mSv (highest quartile relative to lowest quartile), and 35% (95% CI: -1%, 84%) at >109 mSv 15-year lagged dose. The log-linear increase in risk per 100 mSv was 2% (95% CI: -4%, 8%) for unlagged external dose and 5% (95% CI: -2%, 11%) for 15-year lagged dose. Associations with external dose for workers monitored only for exposure to external radiation reflected those previously reported for the cohort from which the cases and controls were drawn. There was little evidence of excess risk associated with cumulative doses from internal sources, which had not been assessed in the cohort study. The impact of the included potential confounding variables was minimal, with the possible exception of occupational noise exposure. Subgroup analyses indicated evidence of heterogeneity between sites, occupational groups and employment duration, and an important factor was whether workers were monitored for the potential presence of internal emitters, which was not explained by other factors included in the study. In summary, we found evidence for an increased IHD mortality risk associated with external radiation dose, but little evidence of an association with internal dose. External dose associations were minimally affected by important confounders. However, the considerable heterogeneity in the associations with external doses observed between subgroups of workers is difficult to explain and requires further work.