| Literature DB >> 22323360 |
Christian C Abnet1, 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 Tang, Jin-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.
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.Entities:
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Year: 2012 PMID： 22323360 PMCID： PMC3315211 DOI： 10.1093/hmg/dds029
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150