title: 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.affiliation: Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Kristin L
authors.initials: KL
authors.lastname: White
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phelan
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Larson
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Beesley
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D010454:Peptide Termination Factors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011808:Quinone Reductases / Q000235:genetics; D012307:Risk Factors; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D010454:Peptide Termination Factors; D015262:Xenobiotics; C087971:peptide-chain-release factor 3; D000426:Alcohol Dehydrogenase; C105552:alcohol dehydrogenase IV; D019363:Cytochrome P-450 CYP1A1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human