A cohort of 94,000 survivors of the Hiroshima and Nagasaki atomic bombings is being studied in collaboration with the Radiation Effects Research Foundation (RERF). Cohort studies are used to quantify radiation dose response and its dependence on histological subtype of tumor, age at exposure, sex, age at observation, and time following exposure. A recently completed study of salivary gland tumors found a marked excess of radiation-related tumors, largely limited to mucoepidermoid carcinoma and Warthin's tumor. Case ascertainment has been completed in studies of tumors of the breast, central nervous system, and ovary, and the data are being analyzed. Relative to age-specific baseline rates, the radiation-related excess risk of breast cancer following exposure at young ages (<20) was considerably higher for diagnosis before age 35 than later; however, it has remained flat thereafter, showing no sign of decline over the interval 35-65 years of age. Furthermore, in modeling the excess relative risk per unit dose as a function of age at exposure, women who were exposed before age 20 have the highest risk; and women who were exposed at 40 years of age or older have the least risk. There is no indication that exposure around the ages of menarche or breast budding carries more risk than exposure during early childhood or late adolescence. Case ascertainment is also underway for lung and lymphoid cancers. A study of hormonal levels in stored serum obtained from women who later developed breast cancer and from similar controls, found a significantly increased risk associated with level of unbound estradiol. A new, very large record-based study of breast cancer has been initiated to verify and refine earlier findings of interactions between reproductive history and radiation dose.A case-case approach is being used to study genetic susceptibility to radiation carcinogenesis and breast cancer. The previously reported phenomenon of extremely high, dose-specific relative risks for early-onset breast cancer (before age 35) is suggestive of increased sensitivity to radiation among a genetically predisposed population subgroup, and an interesting subject for further investigation. A future focus may be on molecular assays for BRCA1, BRCA2, p53, ATM, and other gene mutations in cases or their close relatives.
