DESCRIPTION: Epidemiological studies of US nuclear weapons workers allow evaluation of the effects of low dose, low dose rate radiation exposures accrued in an environment of mixed radiological and non-radiological exposures associated with the USDOE weapons complex. In the proposed study, we will examine a cohort of nearly 22,000 badge-monitored workers at the Savannah River Site (SRS) who will be followed over a fifty-year period. Past research on this epidemiologically important population has focused on analyses of standardized mortality ratios. The proposed study, in contrast, will focus on radiation-mortality associations in this cohort while investigating potential sources of bias and effect modification. We will examine radiation-mortality associations under varying lag assumptions, and investigate potential changes with age-at-exposure in susceptibility to the carcinogenic effects of radiation. Next, we will investigate differences between workers in the carcinogenic effects of radiation exposure due to non-radiological exposures accrued at SRS. Mechanistic models of carcinogenesis suggest that initiating exposure to some non-radiological carcinogens may modify the effects of subsequent ionizing radiation exposures. We will use a job-exposure matrix to identify workers with routine potential for exposure to several non-radiological agents, and apply innovative methods to examine the joint effects of radiological and non-radiological exposures. Finally, we will examine the role of tritium and neutron exposures in these analyses of radiation-mortality associations. We will investigate whether variation in radiation risk estimates between subgroups of workers reflects heterogeneity in radiological exposures. Study results for this large USDOE cohort will be evaluated in relation to observations from studies of other DOE facilities; and, study data will be compiled in a manner that will facilitate future pooled analyses. In this way, the proposed work will substantially strengthen the available epidemiological information about low level radiation effects in USDOE cohorts.