DESCRIPTION (provided by applicant): Among the cancers unique to women, ovarian
cancer has the highest mortality rate. Despite the public health importance of
the disease, the epidemiology is poorly understood. We propose to
systematically test the hypothesis that common genetic polymorphisms for
enzymes that catalyze pathways of estrogen and catechol estrogen formation
represent risk factors for epithelial ovarian cancer. This hypothesis will be
tested in a large case-control study conducted at the Mayo Clinic Rochester,
Mayo Clinic Jacksonville, and Duke University in North Carolina. We anticipate
recruitment of a total of 1372 incident cases (1217 Caucasian and 155 African
American). Clinic based controls matched on age, race, and state of residence
will be identified through General Internal Medicine Clinics at Mayo and
through Random Digit Dialing in North Carolina. Ovarian cancer risk factors
will be obtained through a structured interview with all cases and controls.
Blood samples orbuccal cells will be obtained as a source of DNA to detect
known, functionally significant polymorphisms in genes for cytochrome P450 1A1
(CYP1A1), cytochrome P450 1B1 (CYP1B1), catechol 0-methyltransferase (COMT),
sulfotransferase 1A1 (SULT1A1), glutathione S-transferase (GST) Ml, GST P1, and
GST Ti as well as NAD(P)H:quinone oxidoreductase (NQO1). The analytic approach
entails comparison of frequencies of alleles and genotypes for each of the
genetically polymorphic enzymes studied with: a) expected population allele and
genotype frequencies estimated from age- and race-matched control women using
conditional logistic regression. In addition, we propose to evaluate the extent
that measured non-genetic factors (e.g., reproductive history and oral
contraceptive use) might modify or confound any observed association between
these candidate genes and ovarian cancer risk. There is evidence from the
breast cancer literature that these genetic polymorphisms are important risk
factors. It is innovative, plausible, and important to evaluate similar
associations with epithelial ovarian cancer. The results could have profound
implications for our understanding of the disease.
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