Xenobiotic-Metabolizing gene polymorphisms and ovarian cancer risk

Ellen L. Goode, Kristin L. White, Robert A. Vierkant, Catherine M. Phelan, Julie M. Cunningham, Joellen M. Schildkraut, Andrew Berchuck, Melissa C. Larson, Brooke L. Fridley, Janet E. Olson, Penelope M. Webb, Xiaoqing Chen, Jonathan Beesley, Georgia Chenevix-Trench, Thomas A. Sellers

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Because selected xenobiotic-metabolizing enzymes process pro-carcinogens that could initiate ovarian carcinogenesis, we hypothesized that single nucleotide polymorphisms (SNPs) in the genes encoding xenobiotic-metabolizing enzymes are associated with risk of ovarian cancer. Cases with invasive epithelial ovarian cancer (N=1,571 including 956 of serous sub-type) and controls (N=2,046) from three studies were genotyped at 11 SNPs in EPHX1, ADH4, ADH1A, NQO2, NAT2, GSTP1, CYP1A1, and NQO1, following an initial SNP screen in a subset of participants. Logistic regression analysis of genotypes obtained via Illumina GoldenGate and Sequenom iPlex technologies revealed the following age- and study-adjusted associations: EPHX1 rs1051740 with increased serous ovarian cancer risk [per-allele odds ratio (OR) 1.17, 95% confidence interval (95% CI) 1.04-1.32, P=0.01), ADH4 r1042364 with decreased ovarian cancer risk (OR 0.90, 95% CI: 0.81-1.00, P=0.05), and NQO1 rs291766 with increased ovarian cancer risk (OR 1.11, 95% CI: 1.00-1.23, P=0.04). These findings are consistent with prior studies implicating these genes in carcinogenesis and suggest that this collection of variants is worthy of follow-up in additional studies.

Original languageEnglish (US)
Pages (from-to)397-402
Number of pages6
JournalMolecular Carcinogenesis
Volume50
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Carcinogenesis
  • Epidemiology
  • Gynecologic neoplasia

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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    Goode, E. L., White, K. L., Vierkant, R. A., Phelan, C. M., Cunningham, J. M., Schildkraut, J. M., Berchuck, A., Larson, M. C., Fridley, B. L., Olson, J. E., Webb, P. M., Chen, X., Beesley, J., Chenevix-Trench, G., & Sellers, T. A. (2011). Xenobiotic-Metabolizing gene polymorphisms and ovarian cancer risk. Molecular Carcinogenesis, 50(5), 397-402. https://doi.org/10.1002/mc.20714