Haplotype analysis of CYP11A1 identifies promoter variants associated with breast cancer risk.

Yaspan BL, Breyer JP, Cai Q, Dai Q, Elmore JB, Amundson I, Bradley KM, Shu XO, Gao YT, Dupont WD, Zheng W, Smith JR
Cancer Res. 2007 67 (12): 5673-82

PMID: 17575134 · PMCID: PMC2805128 · DOI:10.1158/0008-5472.CAN-07-0467

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.

MeSH Terms (17)

Adult Asian Continental Ancestry Group Breast Neoplasms Cholesterol Side-Chain Cleavage Enzyme Female Gene Expression Gene Expression Profiling Genetic Predisposition to Disease Haplotypes Humans Linkage Disequilibrium Middle Aged Polymerase Chain Reaction Polymorphism, Genetic Promoter Regions, Genetic Risk Factors Transcription, Genetic

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