RT Journal Article
SR Electronic
T1 Identification of new susceptibility loci for gastric non-cardia adenocarcinoma: pooled results from two Chinese genome-wide association studies
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 581
OP 587
DO 10.1136/gutjnl-2015-310612
VO 66
IS 4
A1 Zhaoming Wang
A1 Juncheng Dai
A1 Nan Hu
A1 Xiaoping Miao
A1 Christian C Abnet
A1 Ming Yang
A1 Neal D Freedman
A1 Jinfei Chen
A1 Laurie Burdette
A1 Xun Zhu
A1 Charles C Chung
A1 Chuanli Ren
A1 Sanford M Dawsey
A1 Meilin Wang
A1 Ti Ding
A1 Jiangbo Du
A1 Yu-Tang Gao
A1 Rong Zhong
A1 Carol Giffen
A1 Wenting Pan
A1 Woon-Puay Koh
A1 Ningbing Dai
A1 Linda M Liao
A1 Caiwang Yan
A1 You-Lin Qiao
A1 Yue Jiang
A1 Xiao-Ou Shu
A1 Jiaping Chen
A1 Chaoyu Wang
A1 Hongxia Ma
A1 Hua Su
A1 Zhendong Zhang
A1 Lemin Wang
A1 Chen Wu
A1 Yong-Bing Xiang
A1 Zhibin Hu
A1 Jian-Min Yuan
A1 Lu Xie
A1 Wei Zheng
A1 Dongxin Lin
A1 Stephen J Chanock
A1 Yongyong Shi
A1 Alisa M Goldstein
A1 Guangfu Jin
A1 Philip R Taylor
A1 Hongbing Shen
YR 2017
UL http://gut.bmj.com/content/66/4/581.abstract
AB 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.