title: Haplotype analysis of CYP11A1 identifies promoter variants associated with breast cancer risk.
abstract: The CYP11A1 gene encodes the cholesterol side chain cleavage enzyme that catalyzes the initial and rate-limiting step of steroidogenesis. A large number of epidemiologic studies have implicated the duration and degree of endogenous estrogen exposure in the development of breast cancer in women. Here, we conduct a systematic investigation of the role of genetic variation of the CYP11A1 gene in breast cancer risk in a study of 1193 breast cancer cases and 1310 matched controls from the Shanghai Breast Cancer Study. We characterize the genetic architecture of the CYP11A1 gene in a Chinese study population. We then genotype tagging polymorphisms to capture common variation at the locus for tests of association. Variants designating a haplotype encompassing the gene promoter are significantly associated with both increased expression (P = 1.6e-6) and increased breast cancer risk: heterozygote age-adjusted odds ratio (OR), 1.51 [95% confidence interval (95% CI), 1.19-1.91]; homozygote age-adjusted OR, 2.94 (95% CI, 1.22-7.12), test for trend, P = 5.0e-5. Among genes controlling endogenous estrogen metabolism, CYP11A1 harbors common variants that may influence expression to significantly modify risk of breast cancer.
authors.affiliation: Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN 37232-0275, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Yaspan
authors.forename: Joan P
authors.initials: JP
authors.lastname: Breyer
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
authors.forename: J Bradford
authors.initials: JB
authors.lastname: Elmore
authors.forename: Isaac
authors.initials: I
authors.lastname: Amundson
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Bradley
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Smith
mesh_terms: D000328:Adult; D044466:Asian People; D001943:Breast Neoplasms / Q000235:genetics*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014158:Transcription, Genetic
chemical_list: D002786:Cholesterol Side-Chain Cleavage Enzyme