Lu Hong, Chen Dong, Hu Li-Ping, Zhou Lian-Lian, Xu Hui-Ying, Bai Yong-Heng, Lin Xiang-Yang
Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China E-mail :
Asian Pac J Cancer Prev. 2014 Jan;14(11):6743-9. doi: 10.7314/apjcp.2013.14.11.6743.
Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene (ESR-α) are associated with breast cancer risk. However, previous results from many molecular studies have been inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-α gene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms and breast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysis of 24 published studies evaluating the association. No significant associations were found between the PvuII polymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observed among carriers of the XbaI 'G' allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers of the 'A' allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the 'CG' haplotype (OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI 'G' allele was associated with an overall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII 'C' allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an association between the PvuII 'C' and XbaI 'G' alleles and breast cancer risk was significant in Asians ('C' vs. 'T': OR = 0.93, 95% CI = 0.85- 1.00; 'G' vs. 'A': OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, our results provide evidence that ESR-α polymorphisms are associated with susceptibility to breast cancer. These associations may largely depend on population characteristics and geographic location.
分子流行病学研究表明，雌激素受体α基因（ESR-α）的基因多态性与乳腺癌风险相关。然而，许多分子研究的先前结果并不一致。在本研究中，我们检测了来自中国的542例乳腺癌病例和1016例对照中ESR-α基因的两种多态性（PvuII和XbaI限制性片段长度多态性）。使用无条件逻辑回归模型计算多态性与乳腺癌风险之间的关联。使用SHEsis软件分析连锁不平衡和单倍型。此外，我们还对24项评估该关联的已发表研究进行了系统的荟萃分析。未发现PvuII多态性与乳腺癌风险之间存在显著关联。然而，与“A”等位基因携带者相比，XbaI“G”等位基因携带者的乳腺癌风险显著降低（年龄调整后的OR = 0.80；95%CI = 0.66 - 0.97）。单倍型分析显示，“CG”单倍型携带者的癌症风险显著降低（OR = 0.79；95%CI = 0.66 - 0.96）。在系统的荟萃分析中，XbaI“G”等位基因与乳腺癌总体风险显著降低相关（OR = 0.90，95%CI = 0.82 - 1.00）。此外，PvuII“C”等位基因的疾病风险降低了0.96倍（95%CI = 0.92 - 0.99）。在亚组分析中，PvuII“C”和XbaI“G”等位基因与乳腺癌风险之间的关联在亚洲人中显著（“C”与“T”：OR = 0.93，95%CI = 0.85 - 1.00；“G”与“A”：OR = 0.82，95%CI = 0.68 - 0.98），但在欧美人群中不显著。因此，我们的结果提供了证据表明ESR-α多态性与乳腺癌易感性相关。这些关联可能在很大程度上取决于人群特征和地理位置。
