) The proposed 5-year Preventive Oncology Research Award (K07) involves three projects using existing data sets to facilitate rapid training in genetic epidemiology. Emphasis is on cancer susceptibility genes and gene environment interactions. The training and experience gained from the proposed research will enable the principal investigator to pursue a long-term career based on gene-environment interactions, in particular ionizing radiation exposure. The first project focuses on familial aggregation of hematologic neoplasms and uses personal and family history of cancer from more than 200 cases (and 200 controls) in an ongoing case-control study of cancer among Ukrainians exposed to Chernobyl radiation. A unique aspect of this study is that cancer cases and their pair-matched controls are being ascertained from two large regions with and without exposure to radiation. As such, there is great interest to test for increased risk of leukemia among exposed and non-exposed first- and second-degree relatives of exposed and non-exposed probands. The second project uses personal and family history of cancer obtained from more than 300 Ashkenasics who were recently screened for BRCA1 and BRCA2 mutations. Among the 300 screened individuals, more than 70 families with significant history of breast-ovarian cancer have been identified. Using these data, the first aim is to confirm an autosomal dominant mode of inheritance of breast ovarian cancer.
The second aim i s to determine if colon or lung cancer aggregates within this population, and if so, to perform segregation analysis to determine the mode of inheritance. Mutation analysis at the adenomatous polyposis coli (APC) susceptibility gene is being planned and could be used for penetrance calculations. The third project addresses linkage analysis with genotype data from 5 families with 25 individuals affected with Peutz-Jeghers syndrome. Two-point lod scores will be generated with fixed recombination fractions using genotype information for 11 polymorphic microsatellite markers on chromosome 19p. Didactic coursework will focus on genetics and human disease, molecular and cellular genetics, genetic epidemiology, statistical genetics, human DNA variation, recombinant DNA technology, and population genetics. Results of this training will thrust the trainee into a productive career in genetic epidemiology with a particular focus on gene-environment interactions.
