Wu Sheng, Cai Jungang, Wang Hong, Zhang Hongwei, Yang Weige
Department of General Surgery, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, People's Republic of China.
PLoS One. 2013 Aug 15;8(8):e72526. doi: 10.1371/journal.pone.0072526. eCollection 2013.
Genome-wide association studies have identified SNP rs11249433 at chromosome 1p11 as a new breast cancer (BC) susceptibility locus in populations of European descent. Since then, the relationship between 1p11- rs11249433 and breast cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 15 studies involving a total of 90,154 cases and 137,238 controls for 1p11-rs11249433 polymorphism to evaluate its effect on genetic susceptibility for breast cancer. An overall random effects odds ratio of 1.09 (95% CI: 1.06-1.12, P<10(-5)) was found for rs11249433-G variant. Significant results were also observed for heterozygous (OR=1.09, 95% CI: 1.05-1.12, P<10(-5)) and homozygote (OR=1.14, 95% CI: 1.08-1.21, P<10(-5)). There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant associations were found among Caucasians. However, no significant associations were detected among East Asian and African populations. In addition, we found that rs11249433 polymorphism on 1p11 confer risk, exclusively for ER-positive tumors with per-allele OR of 1.13 (95% CI: 1.08-1.18; P <10(-5)) compared to ER-negative tumors of 1.01 (95% CI: 0.98-1.04; P=0.49). Similar results were also observed when stratified by PR status. Our findings demonstrated that rs11249433-G allele is a risk-conferring factor for the development of breast cancer, especially in Caucasians.
全基因组关联研究已确定1号染色体1p11上的单核苷酸多态性（SNP）rs11249433是欧洲血统人群中一个新的乳腺癌（BC）易感位点。自那时起，1p11 - rs11249433与乳腺癌之间的关系已在不同种族群体中得到报道；然而，这些研究结果并不一致。为了探究这种不一致性，我们对15项研究进行了荟萃分析，这些研究共纳入了90154例病例和137238例对照，以评估1p11 - rs11249433多态性对乳腺癌遗传易感性的影响。对于rs11249433 - G变异体，总体随机效应比值比为1.09（95%置信区间：1.06 - 1.12，P < 10⁻⁵）。杂合子（比值比 = 1.09，95%置信区间：1.05 - 1.12，P < 10⁻⁵）和纯合子（比值比 = 1.14，95%置信区间：1.08 - 1.21，P < 10⁻⁵）也观察到显著结果。有强有力的证据表明存在异质性，按种族分层后这种异质性在很大程度上消失了。按种族分层后，在白种人中发现了显著关联。然而，在东亚和非洲人群中未检测到显著关联。此外，我们发现1p11上的rs11249433多态性仅对雌激素受体（ER）阳性肿瘤具有风险，与ER阴性肿瘤相比，每等位基因的比值比为1.13（95%置信区间：1.08 - 1.18；P < 10⁻⁵），而ER阴性肿瘤的比值比为1.01（95%置信区间：0.98 - 1.04；P = 0.49）。按孕激素受体（PR）状态分层时也观察到类似结果。我们的研究结果表明，rs11249433 - G等位基因是乳腺癌发生的一个风险因素，尤其是在白种人中。
