Relationship of Genetic Differences to the Development of Chromosome Abnormalities

Greater understanding of the role of individual variation in response to radiation exposure might clarify the inconsistent relationship between radiation dose, intermediate markers of induced DNA damage, and subsequent cancer risk. REB proposes to collaborate with Columbia University and the Southern Urals Biophysics Institute to elucidate the contribution of germline genetic variation to the frequency of chromosomal aberrations in a cohort of Russian nuclear workers with notable and atypical radiation exposures. Our collaborators are utilizing a new biodosimetry method, termed mBAND, to measure intra-chromosomal aberrations, a potentially useful biomarker of exposure to high linear energy transfer radiation such as plutonium. In addition, they will assess inter-chromosomal aberrations using mFISH (multicolor fluorescent insitu hybridization). As factors other than radiation dose may influence aberration frequency, REB proposes to add to this DOE-funded study an investigation of germline genetic variation in DNA repair and other genes in relation to aberration risk. Mayak nuclear workers (n = approximately 350) employed from 1948-72 will receive a short questionnaire and have a blood sample drawn while receiving routine annual medical exams. Germline genotype will be assessed as a risk factor for chromosome aberration frequency. In this study, we have the opportunity to address scientific questions regarding radiation carcinogenesis mechanisms at relatively little cost in a population with rare, higher dose exposures.