1. Identification of new susceptibility loci for gastric non-cardia adenocarcinoma: Pooled results from two Chinese genome-wide association studies
- Author
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Wang, Z, Wang, Z, Dai, J, Hu, N, Miao, X, Abnet, CC, Yang, M, Freedman, ND, Chen, J, Burdette, L, Zhu, X, Chung, CC, Ren, C, Dawsey, SM, Wang, M, Ding, T, Du, J, Gao, YT, Zhong, R, Giffen, C, Pan, W, Koh, WP, Dai, N, Liao, LM, Yan, C, Qiao, YL, Jiang, Y, Shu, XO, Wang, C, Ma, H, Su, H, Zhang, Z, Wang, L, Wu, C, Xiang, YB, Hu, Z, Yuan, JM, Xie, L, Zheng, W, Lin, D, Chanock, SJ, Shi, Y, Goldstein, AM, Jin, G, Taylor, PR, Shen, H, Wang, Z, Wang, Z, Dai, J, Hu, N, Miao, X, Abnet, CC, Yang, M, Freedman, ND, Chen, J, Burdette, L, Zhu, X, Chung, CC, Ren, C, Dawsey, SM, Wang, M, Ding, T, Du, J, Gao, YT, Zhong, R, Giffen, C, Pan, W, Koh, WP, Dai, N, Liao, LM, Yan, C, Qiao, YL, Jiang, Y, Shu, XO, Wang, C, Ma, H, Su, H, Zhang, Z, Wang, L, Wu, C, Xiang, YB, Hu, Z, Yuan, JM, Xie, L, Zheng, W, Lin, D, Chanock, SJ, Shi, Y, Goldstein, AM, Jin, G, Taylor, PR, and Shen, H
- Abstract
© 2017, BMJ Publishing Group. All rights reserved. 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.
- Published
- 2017