Li Taishun, Zhao Jun, Yang Jiaying, Ma Xu, Dai Qiaoyun, Huang Hao, Wang Lina, Liu Pei
Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, China.
National Research Institute for Family Planning, Beijing, China.
PLoS One. 2016 Apr 12;11(4):e0153314. doi: 10.1371/journal.pone.0153314. eCollection 2016.
Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results.
We pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified.
Three SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555-0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730-0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037-2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations.
Rs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk.
雌激素受体基因（ESR1）中的单核苷酸多态性（SNP）在乳腺癌（BC）易感性中起关键作用。全基因组关联研究报告称，ESR1中的SNP与BC易感性相关；然而，近期研究结果并不一致。因此，我们进行了这项荟萃分析以获得更准确和可信的结果。
我们汇总了来自PubMed、EMBASE和Web of Science的已发表文献，并使用固定效应模型和随机效应模型计算了比值比（OR）及95%置信区间（CI），以评估关联强度。共鉴定出20项有关3个相关SNP的病例对照研究和队列研究。
在我们的总体荟萃分析中，ESR1基因的3个SNP，即rs2077647：T>C、rs2228480：G>A和rs3798577：T>C，与BC风险增加无关。按种族进行的分层分析表明，在白种人中，与GG基因型相比，rs2228480的AA基因型与BC风险降低26%相关（OR = 0.740，95%CI：0.555 - 0.987）。rs3798577：T>C变异的C等位基因与亚洲人BC风险降低相关（OR = 0.828，95%CI：0.730 - 0.939），而携带该等位基因的白种人BC风险显著增加（OR = 1.551，95%CI：1.037 - 2.321）。在所有评估的种族人群中，rs2077647与BC风险之间存在无显著意义的关联。
rs3798577与白种人群体中BC风险增加相关，但与亚洲人群体中BC风险降低相关。rs2228480在白种人中具有较大的保护作用，而rs2077647与BC风险无关。
