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

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. DESIG...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963301/
https://www.ncbi.nlm.nih.gov/pubmed/26701879
http://dx.doi.org/10.1136/gutjnl-2015-310612
Descripción
Sumario: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 (P(wilcoxon 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 (P(conditional)=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.