Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: A meta-analysis of genome-wide association studies

Christian C. Abnet, Zhaoming Wang, Xin Song, Nan Hu, Fu You Zhou, Neal D. Freedman, Xue Min Li, Kai Yu, Xiao Ou Shu, Jian Min Yuan, Wei Zheng, Sanford M. Dawsey, Linda M. Liao, Maxwell P. Lee, Ti Ding, You Lin Qiao, Yu Tang Gao, Woon Puay Koh, Yong Bing Xiang, Ze Zhong TangJin Hu Fan, Charles C. Chung, Chaoyu Wang, William Wheeler, Meredith Yeager, Jeff Yuenger, Amy Hutchinson, Kevin B. Jacobs, Carol A. Giffen, Laurie Burdett, Joseph F. Fraumeni, Margaret A. Tucker, Wong Ho Chow, Xue Ke Zhao, Jiang Man Li, Ai Li Li, Liang Dan Sun, Wu Wei, Ji Lin Li, Peng Zhang, Hong Lei Li, Wen Yan Cui, Wei Peng Wang, Zhi Cai Liu, Xia Yang, Wen Jing Fu, Ji Li Cui, Hong Li Lin, Wen Liang Zhu, Min Liu, Xi Chen, Jie Chen, Li Guo, Jing Jing Han, Sheng Li Zhou, Jia Huang, Yue Wu, Chao Yuan, Jing Huang, Ai Fang Ji, Jian Wei Kul, Zhong Min Fan, Jian Po Wang, Dong Yun Zhang, Lian Qun Zhang, Wei Zhang, Yuan Fang Chen, Jing Li Ren, Xiu Min Li, Jin Cheng Dong, Guo Lan Xing, Zhi Gang Guo, Jian Xue Yang, Yi Ming Mao, Yuan Yuan, Er Tao Guo, Wei Zhang, Zhi Chao Hou, Jing Liu, Yan Li, Sa Tang, Jia Chang, Xiu Qin Peng, Min Han, Wan Li Yin, Ya Li Liu, Yan Long Hu, Yu Liu, Liu Qin Yang, Fu Guo Zhu, Xiu Feng Yang, Xiao Shan Feng, Zhou Wang, Yin Li, She Gan Gao, Hai Lin Liu, Ling Yuan, Yan Jin, Yan Rui Zhang, Ilyar Sheyhidin, Feng Li, Bao Ping Chen, Shu Wei Ren, Bin Liu, Dan Li, Gao Fu Zhang, Wen Bin Yue, Chang Wei Feng, Qirenwang Qige, Jian Ting Zhao, Wen Jun Yang, Guang Yan Lei, Long Qi Chen, En Min Li, Li Yan Xu, Zhi Yong Wu, Zhi Qin Bao, Ji Li Chen, Xian Chang Li, Xiang Zhuang, Ying Fa Zhou, Xian Bo Zuo, Zi Ming Dong, Lu Wen Wang, Xue Pin Fan, Jin Wang, Qi Zhou, Guo Shun Ma, Qin Xian Zhang, Hai Liu, Xin Ying Jian, Sin Yong Lian, Jin Sheng Wang, Fu Bao Chang, Chang Dong Lu, Jian Jun Miao, Zhi Guo Chen, Ran Wang, Ming Guo, Zeng Lin Fan, Ping Tao, Tai Jing Liu, Jin Chang Wei, Qing Peng Kong, Lei Fan, Xian Zeng Wang, Fu Sheng Gao, Tian Yun Wang, Dong Xie, Li Wang, Shu Qing Chen, Wan Cai Yang, Jun Yan Hong, Liang Wang, Song Liang Qiu, Alisa M. Goldstein, Zhi Qing Yuan, Stephen J. Chanock, Xue Jun Zhang, Philip R. Taylor, Li Dong Wang

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10 -8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10 -10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants. Published by Oxford University Press 2012.

Original languageEnglish (US)
Article numberdds029
Pages (from-to)2132-2141
Number of pages10
JournalHuman molecular genetics
Volume21
Issue number9
DOIs
StatePublished - May 1 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Abnet, C. C., Wang, Z., Song, X., Hu, N., Zhou, F. Y., Freedman, N. D., Li, X. M., Yu, K., Shu, X. O., Yuan, J. M., Zheng, W., Dawsey, S. M., Liao, L. M., Lee, M. P., Ding, T., Qiao, Y. L., Gao, Y. T., Koh, W. P., Xiang, Y. B., ... Wang, L. D. (2012). Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: A meta-analysis of genome-wide association studies. Human molecular genetics, 21(9), 2132-2141. [dds029]. https://doi.org/10.1093/hmg/dds029