Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer.
Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer.
复制标题
亚洲人的大规模关联分析确定了前列腺癌的新易感位点。
DOI：
10.1038/ncomms9469
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发表时间：
2015-10-07
影响因子：
16.6
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Wang M;Takahashi A;Liu F;Ye D;Ding Q;Qin C;Yin C;Zhang Z;Matsuda K;Kubo M;Na R;Lin X;Jiang H;Ren S;Sun J;Zheng SL;Marchand LL;Isaacs WB;Mo Z;Haiman CA;Sun Y;Nakagawa H;Xu J
全基因组关联研究（GWAS）已经确定了大约100个与前列腺癌风险相关的基因位点。最初从两个亚洲人群的GWAS中发现的这些基因座不到12个，可能是因为亚洲人的这些个体GWAS样本量较小。在这里，我们对来自日本人群（1583例和3386例对照）和中国人群（1417例和1008例对照）的两个GWAS进行了大规模荟萃分析，然后在三个独立的样本集中进行了复制。我们确定了两个独立的前列腺癌易感位点11p15.4 （rs12791447， P=3.59 × 10−8;PPFIBP2）和14q23.2 （rss58262369， P=6.05 × 10−10;ESR2）。PPFIBP2和ESR2的mRNA水平在前列腺肿瘤和配对的正常组织中存在差异表达。我们的研究为亚洲人有限的前列腺癌风险相关变异增加了两个新的基因座，并为前列腺癌的潜在生物学机制提供了重要的见解。基因变异会影响患前列腺癌的风险。在这里，作者对亚洲人群的全基因组关联研究进行了荟萃分析，发现了11p15.4和14q23.2的新易感位点。
Genome-wide association studies (GWAS) have identified ∼100 genetic loci associated with prostate cancer risk. Less than a dozen of these loci were initially identified from GWAS in two Asian populations, likely because of smaller sample sizes of these individual GWAS in Asians. Here, we conduct a large-scale meta-analysis of two GWAS from the Japanese population (1,583 cases and 3,386 controls) and the Chinese population (1,417 cases and 1,008 controls), followed by replication in three independent sample sets. We identify two independent susceptibility loci for prostate cancer at 11p15.4 (rs12791447, P=3.59 × 10−8; PPFIBP2) and 14q23.2 (rs58262369, P=6.05 × 10−10; ESR2). The mRNA levels of PPFIBP2 and ESR2 are differentially expressed in prostate tumours and paired normal tissues. Our study adds two new loci to the limited number of prostate cancer risk-associated variants in Asians and provides important insight into potential biological mechanisms of prostate cancer. Genetic variations influence the risk of prostate cancer. Here, the authors use a meta-analysis of Genome-wide association studies from Asian populations and uncover new susceptibility loci at 11p15.4 and 14q23.2.