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Xenobiotic-Metabolizing gene polymorphisms and ovarian cancer risk

✍ Scribed by 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; the Ovarian Cancer Association Consortium; the Australian Ovarian Cancer Study Group; the Australian Cancer Study (Ovarian Cancer)

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
80 KB
Volume
50
Category
Article
ISSN
0899-1987

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✦ Synopsis

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. © 2010 Wiley‐Liss, Inc.

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