Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.
Division of Public Health Informatics, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, 461-8673, Japan.
Nat Commun. 2020 Jun 24;11(1):3175. doi: 10.1038/s41467-020-16711-w.
Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.
在日本，胰腺癌是导致癌症相关死亡的第四大原因。为了确定风险基因座，我们对包含 2039 名日本胰腺癌患者和 32592 名对照的三项全基因组关联研究进行了荟萃分析。在这里，我们确定了 3 个全基因组显著的基因座（13q12.2、13q22.1 和 16p12.3）（P < 5.0 × 10），其中 16p12.3 在西方人群中尚未报道过。16p12.3 上的先导单核苷酸多态性（SNP）是 rs78193826（比值比=1.46，95%置信区间=1.29-1.66，P = 4.28 × 10），这是一个亚洲特有的、非同义的糖蛋白 2（GP2）基因变异。在另外 10822 名东亚裔的病例和对照中，对选定的 GP2 基因变异与胰腺癌之间的关联进行了复制。使用细胞系进行的功能分析提供了支持 rs78193826 对 KRAS 活性影响的证据。这些发现表明，GP2 基因变异可能与东亚人群的胰腺癌易感性有关。
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