This collaborative project is focused on site-specific epidemiological studies of tumor risk in a cohort of 120,000 Hiroshima and Nagasaki A-bomb survivors followed by the Radiation Effects Research Foundation in Japan, and on more probing, multidisciplinary approaches using RERF resources including stored tissue and other biological materials. A workshop at NCI, in collaboration with the DCEG Genetics Program and attended by 5 scientists from the genetics and molecular biology programs at RERF, was held to explore possible projects. The immediate result was preparation of a research protocol for investigating heritable gene mutations in early-onset breast cancer cases using archival breast tissue samples. The approach was motivated by an earlier finding of a very high excess risk of radiation-induced breast cancer before age 35 among female a-bomb survivors exposed during childhood or adolescence (ERR at 1 Sv = 14, cf 2.5 for risk of later-onset breast cancer in the same group), consistent with the possible existence of a population subset highly susceptible to both baseline and radiation-related breast cancer. Other, related work in progress includes (1) development of a family database for the study cohort, (2) cataloging of available tissue samples from relevant subjects, (3) and immortalization of cell lines from stored and fresh blood specimens. Exchanges of scientists between NCI and RERF also were discussed. More generally, site-specific epidemiological studies in progress are focused on the female breast, CNS, liver, lung, thyroid gland, lung, and lymphatic system; a study of colorectal cancer is planned. Preparations are being made for a second summary analysis (following the first analysis published in 1994), to begin in FY 2000, of radiation-related cancer incidence risk, by site, based on RERF Tumor Registry records from 1958 through 1995. The results of this analysis are expected to be used by national and international expert committees concerned with radiation- related risk. - Ionizing radiation, Risk analysis, Gene- environment interactions, Cohort studies, Case-control studies, - Human Subjects: Interview, Questionaires, or Surveys Only & Human Tissues, Fluids, Cells, etc.
