title: The CYP17A1 -34T > C polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers.
abstract: Exposure to estrogen has a major effect on breast cancer risk. A polymorphism (-34 T > C; rs743572) in the cytochrome P450c17alpha gene (CYP17A1) encoding an enzyme which controls estrogen levels was reportedly associated with breast cancer risk in average risk populations. The effect of this polymorphism on breast or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers has not been thoroughly investigated. With this aim, 2,221 BRCA1 and BRCA2 mutation carriers (1,313 with breast cancer, 279 with ovarian cancer, and 695 asymptomatic carriers), with either BRCA1 (n = 1693) or BRCA2 (n = 528) germline mutations from seven centers were genotyped for the -34 T > C CYP17 polymorphism. Genotyping was accomplished using Taqman allelic discrimination, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or PCR-based restriction-fragment length polymorphism analysis, and limited sequencing. Data were analyzed using Cox proportional hazards models. The hazard ratios (HRs) for breast cancer was 1.02 (95% CI 0.89-1.17, p = 0.74) and 1.10 (95% CI 0.72-1.67, p = 0.66) for BRCA1 and BRCA2 mutation carriers, respectively. The HRs for ovarian cancer were 1.17 (0.94-1.46, p = 0.17) and 0.91 (0.31-2.67, p = 0.86) for BRCA1 and BRCA2 mutation carriers, respectively. Results remained unaltered when the Israeli cohort (primarily Ashkenazim) was evaluated separately. In conclusion, there was no overall evidence for an association of the -34 T > C CYP17 polymorphism with either breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.
authors.affiliation: Institute of Oncology, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Kaufman
authors.forename: Yael
authors.initials: Y
authors.lastname: Laitman
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.forename: Diana
authors.initials: D
authors.lastname: Torres
authors.forename: Ephrat Levy
authors.initials: EL
authors.lastname: Lahad
authors.forename: Rachel
authors.initials: R
authors.lastname: Beeri
authors.forename: Paul
authors.initials: P
authors.lastname: Renbaum
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Tołoczko-Grabarek
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jaworska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Durda
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Sprudle
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Antoniou
authors.initials: A
authors.lastname: Antonis
authors.forename: Csilla
authors.initials: C
authors.lastname: Szabo
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase