Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies
Year: 2012
Type: review
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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/dds029
Authors: 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 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
Institutions: National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Shandong Provincial Hospital, Henan Medical University, Anyang Tumor Hospital, National University of Singapore, Associated Management Services (United States), Cixian People's Hospital, Vanderbilt University, Vanderbilt-Ingram Cancer Center, UPMC Hillman Cancer Center, Pittsburg State University, Center for Cancer Research, Shanxi Provincial Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Shanghai Cancer Institute, Changzhi University, Changzhi Medical College, Science Applications International Corporation (United States), Information Management Services, Linzhou Cancer Hospital, Anhui University, Anhui Medical University, Nanyang Medical College, Zhengzhou University, Second Affiliated Hospital of Zhengzhou University, Henan University of Science and Technology, First Affiliated Hospital of Henan University of Science and Technology, Henan Cancer Hospital, Shangqiu First People's Hospital, Xinxiang Central Hospital, Shandong University, Zhengzhou People's Hospital, Xinjiang Medical University, First Affiliated Hospital of Xinjiang Medical University, Shihezi University, Henan University, Henan University Huaihe Hospital and Huaihe Clinical Institute, Xinyang Central Hospital, Beijing Tongren Hospital, Capital Medical University, Inner Mongolia Medical University, Inner Mongolia Medical College Hospital, Ningxia Medical University, Sichuan University, West China Hospital of Sichuan University, Shantou University, Shantou University Medical College, Third People's Hospital of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, State Key Laboratory of Genetic Resources and Evolution, Shanghai Institutes for Biological Sciences, Zhejiang University, Medical College of Wisconsin, Medical College of Wisconsin Cancer Center
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1060151506, G1073576994, G1116937713, G1259399321, ENVIRONMENTAL EXPOSURES IN CANCER ETIOLOGY, G1826260630, G2176833112, THE SINGAPORE COHORT STUDY OF DIET AND CANCER, G2802736426, Cancer Risk Reduction and Diet: A Cohort Study of Women, Meharry Clinical and Translational Research Center (MeTRC), NUTRITION INTERVENTION TRIALS IN LINXIAN CHINA-CONTINUED, G335053239, G3828336601, G395096460, G4014730521, G4494048110, G4760797969, G515168323, G5689426, G6016538124, 1/3) MMC, VICC, and TSU: Partners in Eliminating Cancer Disparities, G92400254
OpenAlex ID: W2127236929