中国女性中雌激素受体α及雌二醇合成酶基因CYP17和CYP19的基因多态性与乳腺癌风险的关联
Association of genetic polymorphisms of ER-alpha and the estradiol-synthesizing enzyme genes CYP17 and CYP19 with breast cancer risk in Chinese women.
作者信息
Zhang Lina, Gu Lin, Qian Biyun, Hao Xishan, Zhang Wei, Wei Qingyi, Chen Kexin
机构信息
Departments of Breast Oncology/Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China.
出版信息
Breast Cancer Res Treat. 2009 Mar;114(2):327-38. doi: 10.1007/s10549-008-9998-0. Epub 2008 Jul 16.
Estrogen plays a role in breast cancer development, and genetic polymorphisms in estrogen receptor gene ER-alpha and genes regulating estrogen biosynthesis and metabolisms are associated with the risk of breast cancer in women in western countries. Therefore, we hypothesized that SNPs in ER-alpha and other estrogen-metabolizing genes contribute to breast cancer risk in Chinese women. In this study, we genotyped polymorphisms in the regulatory regions of ER-alpha (rs3798577) and other two estrogen-metabolizing enzyme genes CYP17 (rs743572) and CYP19 (rs10046) among 300 breast cancer cases and 390 controls in a Chinese population. Crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses to estimate breast cancer risk associated with these polymorphisms. We found that the T allele frequency of ER-alpha was significantly higher in cases (59.8%) than controls (54.5%) (P = 0.047), but no significant difference was found in the genotype distribution. However, postmenopausal breast cancer risk was associated with the CYP17 TC genotype (aOR = 1.77, 95% CI = 1.11-2.83) compared with the TT genotype. The CYP19 variant TC + TT genotypes were associated with both overall cancer risk (TT + TC vs. TT aOR = 1.73, 95% CI = 1.13-2.65) and premenopausal cancer risk (TT + TC vs. TT aOR = 1.78, 95% CI = 1.03-3.09), particularly for ER +/PR + tumors. Furthermore, there were joint effects between CYP19 T and ER-alpha T variant genotypes (aOR = 1.67, 95% CI = 1.03-2.69 for CYP19 TC + TT vs. CC among ER-alpha T variant carriers) and between CYP19 T and CYP17 C variant genotypes (aOR = 1.77, 95% CI = 1.11-2.83 for CYP19 TC + TT vs. CC among CYP17 variant C carriers). This study provides evidence that polymorphisms CYP17 rs743572, CYP19 rs10046 and ER-alpha rs3798577 are associated with breast cancer risk among Chinese women.
雌激素在乳腺癌发展过程中发挥作用，在西方国家，雌激素受体基因ER-α以及调控雌激素生物合成与代谢的基因中的基因多态性与女性患乳腺癌的风险相关。因此，我们推测ER-α及其他雌激素代谢基因中的单核苷酸多态性（SNPs）与中国女性患乳腺癌的风险有关。在本研究中，我们对中国人群中300例乳腺癌病例和390例对照的ER-α调控区（rs3798577）以及另外两个雌激素代谢酶基因CYP17（rs743572）和CYP19（rs10046）的多态性进行了基因分型。通过无条件逻辑回归分析计算粗比值比（ORs）和调整后的比值比（aORs）以及95%置信区间（CIs），以评估与这些多态性相关的乳腺癌风险。我们发现，ER-α的T等位基因频率在病例组（59.8%）中显著高于对照组（54.5%）（P = 0.047），但基因型分布无显著差异。然而，与TT基因型相比，绝经后乳腺癌风险与CYP17的TC基因型相关（aOR = 1.77，95% CI = 1.11 - 2.83）。CYP19的TC + TT变异基因型与总体癌症风险（TT + TC vs. TT，aOR = 1.73，95% CI = 1.13 - 2.65）和绝经前癌症风险均相关（TT + TC vs. TT，aOR = 1.78，95% CI = 1.03 - 3.09），尤其是对于ER +/PR +肿瘤。此外，CYP19的T与ER-α的T变异基因型之间存在联合效应（在ER-α T变异携带者中，CYP19的TC + TT vs. CC，aOR = 1.67，95% CI = 1.03 - 2.69），CYP19的T与CYP17的C变异基因型之间也存在联合效应（在CYP17变异C携带者中，CYP19的TC + TT vs. CC，aOR = 1.77，95% CI = 1.11 - 2.83）。本研究提供了证据表明，CYP17 rs743572、CYP19 rs10046和ER-α rs3798577的多态性与中国女性患乳腺癌的风险相关。
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