Xenobiotic-Metabolizing gene polymorphisms and ovarian cancer risk.

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 = 1571 including 956 of serous sub-type) and controls (N = 2046) 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.

• Authors: 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, Ovarian Cancer Association Consortium, Australian Ovarian Cancer Study Group
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 50 Issue 5 Pg. 397-402 (May 2011) ISSN: 1098-2744 [Electronic] United States
• PMID: 21480392 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Wiley-Liss, Inc.

Chemical References

• Peptide Termination Factors
• Xenobiotics
• peptide-chain-release factor 3
• Alcohol Dehydrogenase
• alcohol dehydrogenase IV
• Cytochrome P-450 CYP1A1
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, human
• NRH - quinone oxidoreductase2
• Quinone Reductases
• Arylamine N-Acetyltransferase
• NAT2 protein, human
• Epoxide Hydrolases
• EPHX1 protein, human

Topics

• Alcohol Dehydrogenase (genetics)
• Arylamine N-Acetyltransferase (genetics)
• Cytochrome P-450 CYP1A1 (genetics)
• Epoxide Hydrolases (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Humans
• Logistic Models
• Middle Aged
• NAD(P)H Dehydrogenase (Quinone) (genetics)
• Ovarian Neoplasms (genetics, metabolism)
• Peptide Termination Factors (genetics)
• Polymorphism, Single Nucleotide
• Quinone Reductases (genetics)
• Risk Factors
• Xenobiotics (metabolism)