title: Estrogen bioactivation, genetic polymorphisms, and ovarian cancer.
abstract: Recent experimental evidence has shown that catechol estrogens can be activated through metabolism to form depurinating DNA adducts and thereby initiate cancer. Limited data are available regarding this pathway in epithelial ovarian cancer. We conducted a case-control study of 503 incident epithelial ovarian cancer cases at the Mayo Clinic in Rochester, MN, and Jacksonville, FL, and a 48-county region in North Carolina. Six hundred nine cancer-free controls were frequency matched to the cases on age, race, and residence. After an interview to obtain data on risk factors, a sample of blood was collected for DNA isolation. Subjects were genotyped for seven common single nucleotide polymorphisms in four genes involved in catechol estrogen formation (CYP1A1 and CYP1B1) or conjugation (COMT and SULT1A1). Data were analyzed using logistic regression, stratified by race, and with adjustment for design factors and potential confounders. None of the individual genotypes were significantly associated with ovarian cancer risk. However, an oligogenic model that considered the joint effects of the four candidate genes provided evidence for an association between combinations of these genes and ovarian cancer status (P = 0.015). Although preliminary, this study provides some support for the hypothesis that low-penetrance susceptibility alleles may influence risk of epithelial ovarian cancer.
authors.affiliation: Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33602, USA. sellerta@moffitt.usf.edu
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Sellers
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Fredericksen
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.forename: Julie
authors.initials: J
authors.lastname: Cunningham
authors.forename: William
authors.initials: W
authors.lastname: Taylor
authors.forename: Mark
authors.initials: M
authors.lastname: Liebow
authors.forename: Carol
authors.initials: C
authors.lastname: McPherson
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
authors.forename: Tuya
authors.initials: T
authors.lastname: Pal
authors.forename: Araba A
authors.initials: AA
authors.lastname: Adjei
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D004967:Estrogens