Major risk factors known to be linked to ovarian cancer include early age at menarche, no use of oral contraceptive pills, infertility, and nulliparity. These all suggest an association with hormonal factors in the etiology of ovarian cancer. Low malignant potential (LMP) tumors appear to have similar epidemiological patterns with respect to reproductive events as their more malignant counterparts. Preliminary data suggests that there is a significant ethnic variation in the incidence, histology and age at diagnosis of LMP ovarian tumors in comparison to invasive epithelial ovarian cancers. Presumably the difference in the presentation of LMP ovarian tumors between ethnic groups is the result of distinct hormonal influences. New etiologic hypotheses are needed to evaluate the factors that promote susceptibility to invasive epithelial ovarian cancer and ovarian LMP tumors as compared to unaffected women. Levels of estrogens are the result of a complex regulation process including biosynthesis and degradation mediated by an array of enzyme systems. Our hypothesis is that functionally relevant sequence variants in genes involved in steroid hormone metabolism (metabolic genetic factors; estrogen metabolism genes, specifically cytochrome P450c17alpha (CYP17) gene, the aromatase (CYP19) gene and COMT) act together, and also interact with well-known hormonally related risk factors, to define a risk profile for tow malignant potential ovarian tumors and invasive epithelial ovarian cancers in comparison to unaffected control subjects. In this study we propose a case-control design where the cases are 250 epithelial ovarian cancer subjects and 250 LMP ovarian tumors subjects. All the controls will be population-based unaffected female subjects. Data on hormonal factors will be collected from cases and controls, and blood samples will be obtained. Comparisons will be made to measure if the risks of LMP and ovarian cancers are associated with hormonal exposures and mediated by the variability of estrogen metabolism genes. Advances in the conceptual knowledge of the factors that promote the development of low malignant potential tumors versus invasive ovarian cancer might influence screening and modify the risk of both of these ovarian malignancies.
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