Data from: Common genetic variation in ETV6 is associated with colorectal cancer susceptibility

Genome-wide association studies (GWAS) have identified multiple susceptibility loci for colorectal cancer, but much of heritability remains unexplained. To identify additional susceptibility loci for colorectal cancer, here we perform a GWAS in 1,023 cases and 1,306 controls and replicate the findings in seven independent samples from China, comprising 5,317 cases and 6,887 controls. We find a variant at 12p13.2 associated with colorectal cancer risk (rs2238126 in ETV6, P = 2.67 × 10-10). We replicate this association in an additional 1,046 cases and 1,076 controls of European ancestry (P = 0.034). The G allele of rs2238126 confers earlier age at onset of colorectal cancer (P = 1.98 × 10-6) and reduces the binding affinity of transcriptional enhancer MAX. The mRNA level of ETV6 is significantly lower in colorectal tumors than in paired normal tissues. Our findings highlight the potential importance of genetic variation in ETV6 conferring susceptibility to colorectal cancer.全基因组关联分析（Genome-wide association studies, GWAS）已成功识别出多个结直肠癌易感基因座，但仍有大量遗传力尚未得到阐明。为识别更多结直肠癌易感基因座，本研究纳入1023例结直肠癌患者与1306例健康对照开展全基因组关联分析，并在7个独立的中国人群样本中对研究结果进行验证，该验证队列共包含5317例病例与6887例对照。本研究在12p13.2位点发现一个与结直肠癌风险相关的变异（ETV6基因内的rs2238126，P=2.67×10^-10）。在另一组包含1046例欧洲血统结直肠癌患者与1076例健康对照的队列中，我们再次验证了该变异与结直肠癌风险的关联（P=0.034）。rs2238126的G等位基因可使结直肠癌患者的发病年龄提前（P=1.98×10^-6），同时会降低转录增强子MAX的结合亲和力。结直肠癌肿瘤组织中ETV6的mRNA表达水平显著低于配对的正常组织。本研究结果表明，ETV6基因的遗传变异在结直肠癌易感机制中具有潜在重要作用。