MOLECULAR EPIDEMIOLOGY OF OVARIAN CANCER

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DESCRIPTION: This is an application for a population-based, case-control study of ovarian cancer in North Carolina. It proposes to conduct home interviews and take blood from 700 new cases, identified through a rapid reporting system, and 700 controls, identified through random digit dialing (RDD) and Health Care Financing Administration (HCFA) files. Tumor tissues will be tested for p53 mutations and for HER-2/neu amplification: the first using immunohistochemical staining supplemented by sequencing; and the second using FISH. Genomic DNA will be tested for polymorphisms in the genes for TP53, H-Ras, CYP17 and epoxide hydrolase. The general hypothesis is that ovarian cancer is a heterogeneous disease caused by several different mutational pathways. The application proposes to test this by analyzing subgroups of the data defined by tumors with or without mutations in p53, different histologic types and different polymorphisms. Published preliminary studies have already shown an association with abnormal expression of p53 in ovarian tumors and epidemiologic markers of ovulation.