Yaspan Brian L, Breyer Joan P, Cai Qiuyin, Dai Qi, Elmore J Bradford, Amundson Isaac, Bradley Kevin M, Shu Xiao-Ou, Gao Yu-Tang, Dupont William D, Zheng Wei, Smith Jeffrey R
Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, TN 37232-0275, USA.
Cancer Res. 2007 Jun 15;67(12):5673-82. 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.
CYP11A1基因编码胆固醇侧链裂解酶，该酶催化类固醇生成的起始步骤和限速步骤。大量流行病学研究表明，内源性雌激素暴露的持续时间和程度与女性乳腺癌的发生有关。在此，我们在一项来自上海乳腺癌研究的1193例乳腺癌病例和1310例匹配对照的研究中，对CYP11A1基因的遗传变异在乳腺癌风险中的作用进行了系统研究。我们在中国研究人群中对CYP11A1基因的遗传结构进行了表征。然后，我们对标签多态性进行基因分型，以捕捉该位点的常见变异用于关联测试。指定包含基因启动子的单倍型的变异与表达增加（P = 1.6e - 6）和乳腺癌风险增加均显著相关：杂合子年龄调整优势比（OR）为1.51 [95%置信区间（95%CI），1.19 - 1.91]；纯合子年龄调整OR为2.94（95%CI，1.22 - 7.12），趋势检验P = 5.0e - 5。在内源性雌激素代谢的控制基因中，CYP11A1含有可能影响表达从而显著改变乳腺癌风险的常见变异。
