Identification of new susceptibility loci for gastric non-cardia adenocarcinoma: Pooled results from two Chinese genome-wide association studies

Zhaoming Wang, Juncheng Dai, Nan Hu, Xiaoping Miao, Christian C. Abnet, Ming Yang, Neal D. Freedman, Jinfei Chen, Laurie Burdette, Xun Zhu, Charles C. Chung, Chuanli Ren, Sanford M. Dawsey, Meilin Wang, Ti Ding, Jiangbo Du, Yu Tang Gao, Rong Zhong, Carol Giffen, Wenting PanWoon Puay Koh, Ningbing Dai, Linda M. Liao, Caiwang Yan, You Lin Qiao, Yue Jiang, Xiao Ou Shu, Jiaping Chen, Chaoyu Wang, Hongxia Ma, Hua Su, Zhendong Zhang, Lemin Wang, Chen Wu, Yong Bing Xiang, Zhibin Hu, Jian Min Yuan, Lu Xie, Wei Zheng, Dongxin Lin, Stephen J. Chanock, Yongyong Shi, Alisa M. Goldstein, Guangfu Jin, Philip R. Taylor, Hongbing Shen

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Abstract

Objective 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. Design 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. Results 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=1.21×10-11). This single-nucleotide polymorphism (SNP) marker maps to the intron of the long non-coding RNA, lnc-POLR3G-4 (XLOC_004464), which we observed has lower expression in non-cardia gastric tumour compared with matched normal tissue (Pwilcoxon signed-rank=7.20×10-4). We also identified a new signal at the 1q22 locus, rs80142782 (per-allele OR=0.62; 95% CI 0.56 to 0.69; p=1.71×10-19), 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=6.28×10-17). Analysis of the new SNP conditioned on the known SNP showed that the new SNP remained genome-wide significant (Pconditional=3.47×10-8). Interestingly, rs80142782 has a minor allele frequency of 0.05 in East Asians but is monomorphic in both European and African populations. Conclusion 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.

Original languageEnglish (US)
JournalGut
DOIs
Publication statusAccepted/In press - Dec 23 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Gastroenterology

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