Wang Zhaoming, Dai Juncheng, Hu Nan, Miao Xiaoping, Abnet Christian C, Yang Ming, Freedman Neal D, Chen Jinfei, Burdette Laurie, Zhu Xun, Chung Charles C, Ren Chuanli, Dawsey Sanford M, Wang Meilin, Ding Ti, Du Jiangbo, Gao Yu-Tang, Zhong Rong, Giffen Carol, Pan Wenting, Koh Woon-Puay, Dai Ningbing, Liao Linda M, Yan Caiwang, Qiao You-Lin, Jiang Yue, Shu Xiao-Ou, Chen Jiaping, Wang Chaoyu, Ma Hongxia, Su Hua, Zhang Zhendong, Wang Lemin, Wu Chen, Xiang Yong-Bing, Hu Zhibin, Yuan Jian-Min, Xie Lu, Zheng Wei, Lin Dongxin, Chanock Stephen J, Shi Yongyong, Goldstein Alisa M, Jin Guangfu, Taylor Philip R, Shen Hongbing
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, MD, USA.
Gut. 2017 Apr;66(4):581-587. doi: 10.1136/gutjnl-2015-310612. Epub 2015 Dec 23.
Although several genome-wide association studies (GWAS) of non-cardia gastric cancer have been published, more novel association signals could be exploited by combining individual studies together, which will further elucidate the genetic susceptibility of non-cardia gastric cancer.
We conducted a meta-analysis of two published Chinese GWAS studies (2031 non-cardia gastric cancer cases and 4970 cancer-free controls) and followed by genotyping of additional 3564 cases and 4637 controls in two stages.
The overall meta-analysis revealed two new association signals. The first was a novel locus at 5q14.3 and marked by rs7712641 (per-allele OR=0.84, 95% CI 0.80 to 0.88; p=1.21×10). This single-nucleotide polymorphism (SNP) marker maps to the intron of the long non-coding RNA, lnc-POLR3G-4 (), which we observed has lower expression in non-cardia gastric tumour compared with matched normal tissue (P=7.20×10). We also identified a new signal at the 1q22 locus, rs80142782 (per-allele OR=0.62; 95% CI 0.56 to 0.69; p=1.71×10), which was independent of the previously reported SNP at the same locus, rs4072037 (per-allele OR=0.74; 95% CI 0.69 to 0.79; p=6.28×10). Analysis of the new SNP conditioned on the known SNP showed that the new SNP remained genome-wide significant (P=3.47×10). Interestingly, rs80142782 has a minor allele frequency of 0.05 in East Asians but is monomorphic in both European and African populations.
These findings add new evidence for inherited genetic susceptibility to non-cardia gastric cancer and provide further clues to its aetiology in the Han Chinese population.
尽管已经发表了几项关于非贲门胃癌的全基因组关联研究（GWAS），但将个体研究合并在一起可以发现更多新的关联信号，这将进一步阐明非贲门胃癌的遗传易感性。
我们对两项已发表的中国GWAS研究（2031例非贲门胃癌病例和4970例无癌对照）进行了荟萃分析，随后分两个阶段对另外3564例病例和4637例对照进行基因分型。
总体荟萃分析揭示了两个新的关联信号。第一个是位于5q14.3的一个新位点，由rs7712641标记（每个等位基因的比值比[OR]=0.84，95%可信区间[CI]为0.80至0.88；p=1.21×10）。这个单核苷酸多态性（SNP）标记定位于长链非编码RNA lnc-POLR3G-4的内含子中，我们观察到与匹配的正常组织相比，该长链非编码RNA在非贲门胃肿瘤中的表达较低（P=7.20×10）。我们还在1q
