Estrogen bioactivation, genetic polymorphisms, and ovarian cancer.

Journal Article (Journal Article;Multicenter Study)

Recent experimental evidence has shown that catechol estrogens can be activated through metabolism to form depurinating DNA adducts and thereby initiate cancer. Limited data are available regarding this pathway in epithelial ovarian cancer. We conducted a case-control study of 503 incident epithelial ovarian cancer cases at the Mayo Clinic in Rochester, MN, and Jacksonville, FL, and a 48-county region in North Carolina. Six hundred nine cancer-free controls were frequency matched to the cases on age, race, and residence. After an interview to obtain data on risk factors, a sample of blood was collected for DNA isolation. Subjects were genotyped for seven common single nucleotide polymorphisms in four genes involved in catechol estrogen formation (CYP1A1 and CYP1B1) or conjugation (COMT and SULT1A1). Data were analyzed using logistic regression, stratified by race, and with adjustment for design factors and potential confounders. None of the individual genotypes were significantly associated with ovarian cancer risk. However, an oligogenic model that considered the joint effects of the four candidate genes provided evidence for an association between combinations of these genes and ovarian cancer status (P = 0.015). Although preliminary, this study provides some support for the hypothesis that low-penetrance susceptibility alleles may influence risk of epithelial ovarian cancer.

Full Text

Duke Authors

Cited Authors

  • Sellers, TA; Schildkraut, JM; Pankratz, VS; Vierkant, RA; Fredericksen, ZS; Olson, JE; Cunningham, J; Taylor, W; Liebow, M; McPherson, C; Hartmann, LC; Pal, T; Adjei, AA

Published Date

  • November 2005

Published In

Volume / Issue

  • 14 / 11 Pt 1

Start / End Page

  • 2536 - 2543

PubMed ID

  • 16284375

International Standard Serial Number (ISSN)

  • 1055-9965

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-05-0142


  • eng

Conference Location

  • United States