Genetic variants at 5p15 are associated with risk and early onset of gastric cancer in Chinese populations
Genetic variants at 5p15 are associated with risk and early onset of gastric cancer in Chinese populations
复制标题
5p15 的遗传变异与中国人群胃癌的风险和早期发病相关
DOI：
10.1093/carcin/bgt259
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发表时间：
2013-11-01
期刊：
影响因子：
4.7
通讯作者：
Jin, Guangfu
中科院分区：
文献类型：
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作者：
Du, Jiangbo;Xu, Yaochu;Jin, Guangfu
5p15的基因变异与多种癌症的风险有关，这表明对癌症的多效性作用。我们假设5p15的基因变异在胃癌的发生发展中起重要作用。为了验证这一假设，我们基于我们现有的胃癌全基因组关联研究(GWAS)数据集(1006例患者和2273名对照)，评估了5p15基因变异与胃癌的相关性，并在一项独立的病例对照研究中复制了两个有希望的基因座，包括1681例胃癌病例和1705名对照。我们发现rs10052016与胃癌的风险在GWAS发现阶段(优势比[OR]0.69，95%可信区间[95%CI]0.550.87)和复制期(优势比0.80，95%CI 0.680.94)一致相关。结合这两项研究，我们发现rs10052016(位于TERT上游132kb)的G等位基因与降低患胃癌的风险显著相关(OR 0.76，95%CI 0.670.87，P5.35 10(5))。此外，rs10052016-G的保护性等位基因也与晚期胃癌发病显著相关(P<0.013)。综上所述，这些发现表明5p15的基因变异可能有助于胃癌的易感性，并可能进一步加深我们对5p15基因座在癌症发生中的理解。
Genetic variants at 5p15 have been associated with multiple cancers risk, suggesting pleiotropic effect on cancer. We hypothesized that genetic variants at 5p15 are important in the development of gastric cancer. To test this hypothesis, we evaluated the associations of genetic variants at 5p15 with gastric cancer based on our existing genome-wide association study (GWAS) data set of gastric cancer (1006 cases and 2273 controls), and replicated two promising loci in an independent casecontrol study with 1681 gastric cancer cases and 1705 controls in a Chinese population. We found that rs10052016 was consistently associated with gastric cancer risk in GWAS discovery stage (odds ratio [OR] 0.69, 95% confidence interval [95% CI] 0.550.87) and replication stage (OR 0.80, 95% CI 0.680.94). After combining these two studies, we found that the G allele of rs10052016 (at 132 kb upstream of TERT) was significantly associated with a decreased risk of gastric cancer (OR 0.76, 95% CI 0.670.87, P 5.35 10(5)). Moreover, the protective allele of rs10052016-G was also significantly associated with late onset of gastric cancer (P 0.013). In summary, these findings indicate that genetic variants at 5p15 may contribute to gastric cancer susceptibility and may further advance our understanding of 5p15 locus in cancer development.