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