Relationship of Genetic Differences to the Development of Chromosome Abnormalities

Overview

This is a collaborative study by the National Cancer Institute, Columbia University, and the Southern Urals Biophysics Institute in Russia. It will examine the relationship of differences in certain genes to the development of chromosomal abnormalities in workers at the Mayak nuclear production plant in Ozyorsk, Russia. This population was exposed to higher radiation doses from external and internal sources than those received by their counterparts in other countries or considered permissible today. If a risk relationship is found between genetic differences and chromosome abnormalities, the information might be useful in studies designed to examine how high radiation exposures cause cancer. Radiation-exposed Mayak workers employed from 1948 to 1972 in the three Ozyorsk plants directly related to nuclear weapons production may be eligible for this study. They must have remained local residents in the area and estimates of their external and internal radiation exposures must be available. Participants provide a blood sample for genetic studies and answer a questionnaire that includes demographic information and information about their family health history, history of benign tumors, if any, and history of smoking and alcohol consumption. Additional information is collected from patients' medical records. ...

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.