TY - JOUR
T1 - Xenobiotic-Metabolizing gene polymorphisms and ovarian cancer risk
AU - Goode, Ellen L.
AU - White, Kristin L.
AU - Vierkant, Robert A.
AU - Phelan, Catherine M.
AU - Cunningham, Julie M.
AU - Schildkraut, Joellen M.
AU - Berchuck, Andrew
AU - Larson, Melissa C.
AU - Fridley, Brooke L.
AU - Olson, Janet E.
AU - Webb, Penelope M.
AU - Chen, Xiaoqing
AU - Beesley, Jonathan
AU - Chenevix-Trench, Georgia
AU - Sellers, Thomas A.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Carcinogenesis
KW - Epidemiology
KW - Gynecologic neoplasia
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U2 - 10.1002/mc.20714
DO - 10.1002/mc.20714
M3 - Article
C2 - 21480392
AN - SCOPUS:79953772540
SN - 0899-1987
VL - 50
SP - 397
EP - 402
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 5
ER -