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

40 Citations (Scopus)

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

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Genome-Wide Association Study
Single Nucleotide Polymorphism
Meta-Analysis
China
Haplotypes
Esophageal Squamous Cell Carcinoma
Genome
Linkage Disequilibrium
Esophageal Neoplasms
Genetic Recombination
Odds Ratio
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Abnet, C. C., Wang, Z., Song, X., Hu, N., Zhou, F. Y., Freedman, N. D., ... 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
Abnet, Christian C. ; Wang, Zhaoming ; Song, Xin ; Hu, Nan ; Zhou, Fu You ; Freedman, Neal D. ; Li, Xue Min ; Yu, Kai ; Shu, Xiao Ou ; Yuan, Jian Min ; Zheng, Wei ; Dawsey, Sanford M. ; Liao, Linda M. ; Lee, Maxwell P. ; Ding, Ti ; Qiao, You Lin ; Gao, Yu Tang ; Koh, Woon Puay ; Xiang, Yong Bing ; Tang, Ze Zhong ; Fan, Jin Hu ; Chung, Charles C. ; Wang, Chaoyu ; Wheeler, William ; Yeager, Meredith ; Yuenger, Jeff ; Hutchinson, Amy ; Jacobs, Kevin B. ; Giffen, Carol A. ; Burdett, Laurie ; Fraumeni, Joseph F. ; Tucker, Margaret A. ; Chow, Wong Ho ; Zhao, Xue Ke ; Li, Jiang Man ; Li, Ai Li ; Sun, Liang Dan ; Wei, Wu ; Li, Ji Lin ; Zhang, Peng ; Li, Hong Lei ; Cui, Wen Yan ; Wang, Wei Peng ; Liu, Zhi Cai ; Yang, Xia ; Fu, Wen Jing ; Cui, Ji Li ; Lin, Hong Li ; Zhu, Wen Liang ; Liu, Min ; Chen, Xi ; Chen, Jie ; Guo, Li ; Han, Jing Jing ; Zhou, Sheng Li ; Huang, Jia ; Wu, Yue ; Yuan, Chao ; Huang, Jing ; Ji, Ai Fang ; Kul, Jian Wei ; Fan, Zhong Min ; Wang, Jian Po ; Zhang, Dong Yun ; Zhang, Lian Qun ; Zhang, Wei ; Chen, Yuan Fang ; Ren, Jing Li ; Li, Xiu Min ; Dong, Jin Cheng ; Xing, Guo Lan ; Guo, Zhi Gang ; Yang, Jian Xue ; Mao, Yi Ming ; Yuan, Yuan ; Guo, Er Tao ; Zhang, Wei ; Hou, Zhi Chao ; Liu, Jing ; Li, Yan ; Tang, Sa ; Chang, Jia ; Peng, Xiu Qin ; Han, Min ; Yin, Wan Li ; Liu, Ya Li ; Hu, Yan Long ; Liu, Yu ; Yang, Liu Qin ; Zhu, Fu Guo ; Yang, Xiu Feng ; Feng, Xiao Shan ; Wang, Zhou ; Li, Yin ; Gao, She Gan ; Liu, Hai Lin ; Yuan, Ling ; Jin, Yan ; Zhang, Yan Rui ; Sheyhidin, Ilyar ; Li, Feng ; Chen, Bao Ping ; Ren, Shu Wei ; Liu, Bin ; Li, Dan ; Zhang, Gao Fu ; Yue, Wen Bin ; Feng, Chang Wei ; Qige, Qirenwang ; Zhao, Jian Ting ; Yang, Wen Jun ; Lei, Guang Yan ; Chen, Long Qi ; Li, En Min ; Xu, Li Yan ; Wu, Zhi Yong ; Bao, Zhi Qin ; Chen, Ji Li ; Li, Xian Chang ; Zhuang, Xiang ; Zhou, Ying Fa ; Zuo, Xian Bo ; Dong, Zi Ming ; Wang, Lu Wen ; Fan, Xue Pin ; Wang, Jin ; Zhou, Qi ; Ma, Guo Shun ; Zhang, Qin Xian ; Liu, Hai ; Jian, Xin Ying ; Lian, Sin Yong ; Wang, Jin Sheng ; Chang, Fu Bao ; Lu, Chang Dong ; Miao, Jian Jun ; Chen, Zhi Guo ; Wang, Ran ; Guo, Ming ; Fan, Zeng Lin ; Tao, Ping ; Liu, Tai Jing ; Wei, Jin Chang ; Kong, Qing Peng ; Fan, Lei ; Wang, Xian Zeng ; Gao, Fu Sheng ; Wang, Tian Yun ; Xie, Dong ; Wang, Li ; Chen, Shu Qing ; Yang, Wan Cai ; Hong, Jun Yan ; Wang, Liang ; Qiu, Song Liang ; Goldstein, Alisa M. ; Yuan, Zhi Qing ; Chanock, Stephen J. ; Zhang, Xue Jun ; Taylor, Philip R. ; Wang, Li Dong. / Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China : A meta-analysis of genome-wide association studies. In: Human molecular genetics. 2012 ; Vol. 21, No. 9. pp. 2132-2141.
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title = "Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: A meta-analysis of genome-wide association studies",
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.",
author = "Abnet, {Christian C.} and Zhaoming Wang and Xin Song and Nan Hu and Zhou, {Fu You} and Freedman, {Neal D.} and Li, {Xue Min} and Kai Yu and Shu, {Xiao Ou} and Yuan, {Jian Min} and Wei Zheng and Dawsey, {Sanford M.} and Liao, {Linda M.} and Lee, {Maxwell P.} and Ti Ding and Qiao, {You Lin} and Gao, {Yu Tang} and Koh, {Woon Puay} and Xiang, {Yong Bing} and Tang, {Ze Zhong} and Fan, {Jin Hu} and Chung, {Charles C.} and Chaoyu Wang and William Wheeler and Meredith Yeager and Jeff Yuenger and Amy Hutchinson and Jacobs, {Kevin B.} and Giffen, {Carol A.} and Laurie Burdett and Fraumeni, {Joseph F.} and Tucker, {Margaret A.} and Chow, {Wong Ho} and Zhao, {Xue Ke} and Li, {Jiang Man} and Li, {Ai Li} and Sun, {Liang Dan} and Wu Wei and Li, {Ji Lin} and Peng Zhang and Li, {Hong Lei} and Cui, {Wen Yan} and Wang, {Wei Peng} and Liu, {Zhi Cai} and Xia Yang and Fu, {Wen Jing} and Cui, {Ji Li} and Lin, {Hong Li} and Zhu, {Wen Liang} and Min Liu and Xi Chen and Jie Chen and Li Guo and Han, {Jing Jing} and Zhou, {Sheng Li} and Jia Huang and Yue Wu and Chao Yuan and Jing Huang and Ji, {Ai Fang} and Kul, {Jian Wei} and Fan, {Zhong Min} and Wang, {Jian Po} and Zhang, {Dong Yun} and Zhang, {Lian Qun} and Wei Zhang and Chen, {Yuan Fang} and Ren, {Jing Li} and Li, {Xiu Min} and Dong, {Jin Cheng} and Xing, {Guo Lan} and Guo, {Zhi Gang} and Yang, {Jian Xue} and Mao, {Yi Ming} and Yuan Yuan and Guo, {Er Tao} and Wei Zhang and Hou, {Zhi Chao} and Jing Liu and Yan Li and Sa Tang and Jia Chang and Peng, {Xiu Qin} and Min Han and Yin, {Wan Li} and Liu, {Ya Li} and Hu, {Yan Long} and Yu Liu and Yang, {Liu Qin} and Zhu, {Fu Guo} and Yang, {Xiu Feng} and Feng, {Xiao Shan} and Zhou Wang and Yin Li and Gao, {She Gan} and Liu, {Hai Lin} and Ling Yuan and Yan Jin and Zhang, {Yan Rui} and Ilyar Sheyhidin and Feng Li and Chen, {Bao Ping} and Ren, {Shu Wei} and Bin Liu and Dan Li and Zhang, {Gao Fu} and Yue, {Wen Bin} and Feng, {Chang Wei} and Qirenwang Qige and Zhao, {Jian Ting} and Yang, {Wen Jun} and Lei, {Guang Yan} and Chen, {Long Qi} and Li, {En Min} and Xu, {Li Yan} and Wu, {Zhi Yong} and Bao, {Zhi Qin} and Chen, {Ji Li} and Li, {Xian Chang} and Xiang Zhuang and Zhou, {Ying Fa} and Zuo, {Xian Bo} and Dong, {Zi Ming} and Wang, {Lu Wen} and Fan, {Xue Pin} and Jin Wang and Qi Zhou and Ma, {Guo Shun} and Zhang, {Qin Xian} and Hai Liu and Jian, {Xin Ying} and Lian, {Sin Yong} and Wang, {Jin Sheng} and Chang, {Fu Bao} and Lu, {Chang Dong} and Miao, {Jian Jun} and Chen, {Zhi Guo} and Ran Wang and Ming Guo and Fan, {Zeng Lin} and Ping Tao and Liu, {Tai Jing} and Wei, {Jin Chang} and Kong, {Qing Peng} and Lei Fan and Wang, {Xian Zeng} and Gao, {Fu Sheng} and Wang, {Tian Yun} and Dong Xie and Li Wang and Chen, {Shu Qing} and Yang, {Wan Cai} and Hong, {Jun Yan} and Liang Wang and Qiu, {Song Liang} and Goldstein, {Alisa M.} and Yuan, {Zhi Qing} and Chanock, {Stephen J.} and Zhang, {Xue Jun} and Taylor, {Philip R.} and Wang, {Li Dong}",
year = "2012",
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doi = "10.1093/hmg/dds029",
language = "English (US)",
volume = "21",
pages = "2132--2141",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
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}

Abnet, CC, Wang, Z, Song, X, Hu, N, Zhou, FY, Freedman, ND, Li, XM, Yu, K, Shu, XO, Yuan, JM, Zheng, W, Dawsey, SM, Liao, LM, Lee, MP, Ding, T, Qiao, YL, Gao, YT, Koh, WP, Xiang, YB, Tang, ZZ, Fan, JH, Chung, CC, Wang, C, Wheeler, W, Yeager, M, Yuenger, J, Hutchinson, A, Jacobs, KB, Giffen, CA, Burdett, L, Fraumeni, JF, Tucker, MA, Chow, WH, Zhao, XK, Li, JM, Li, AL, Sun, LD, Wei, W, Li, JL, Zhang, P, Li, HL, Cui, WY, Wang, WP, Liu, ZC, Yang, X, Fu, WJ, Cui, JL, Lin, HL, Zhu, WL, Liu, M, Chen, X, Chen, J, Guo, L, Han, JJ, Zhou, SL, Huang, J, Wu, Y, Yuan, C, Huang, J, Ji, AF, Kul, JW, Fan, ZM, Wang, JP, Zhang, DY, Zhang, LQ, Zhang, W, Chen, YF, Ren, JL, Li, XM, Dong, JC, Xing, GL, Guo, ZG, Yang, JX, Mao, YM, Yuan, Y, Guo, ET, Zhang, W, Hou, ZC, Liu, J, Li, Y, Tang, S, Chang, J, Peng, XQ, Han, M, Yin, WL, Liu, YL, Hu, YL, Liu, Y, Yang, LQ, Zhu, FG, Yang, XF, Feng, XS, Wang, Z, Li, Y, Gao, SG, Liu, HL, Yuan, L, Jin, Y, Zhang, YR, Sheyhidin, I, Li, F, Chen, BP, Ren, SW, Liu, B, Li, D, Zhang, GF, Yue, WB, Feng, CW, Qige, Q, Zhao, JT, Yang, WJ, Lei, GY, Chen, LQ, Li, EM, Xu, LY, Wu, ZY, Bao, ZQ, Chen, JL, Li, XC, Zhuang, X, Zhou, YF, Zuo, XB, Dong, ZM, Wang, LW, Fan, XP, Wang, J, Zhou, Q, Ma, GS, Zhang, QX, Liu, H, Jian, XY, Lian, SY, Wang, JS, Chang, FB, Lu, CD, Miao, JJ, Chen, ZG, Wang, R, Guo, M, Fan, ZL, Tao, P, Liu, TJ, Wei, JC, Kong, QP, Fan, L, Wang, XZ, Gao, FS, Wang, TY, Xie, D, Wang, L, Chen, SQ, Yang, WC, Hong, JY, Wang, L, Qiu, SL, Goldstein, AM, Yuan, ZQ, Chanock, SJ, Zhang, XJ, Taylor, PR & Wang, LD 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, vol. 21, no. 9, dds029, pp. 2132-2141. https://doi.org/10.1093/hmg/dds029

Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China : A meta-analysis of genome-wide association studies. / Abnet, Christian C.; Wang, Zhaoming; Song, Xin; Hu, Nan; Zhou, Fu You; Freedman, Neal D.; Li, Xue Min; Yu, Kai; Shu, Xiao Ou; Yuan, Jian Min; Zheng, Wei; Dawsey, Sanford M.; Liao, Linda M.; Lee, Maxwell P.; Ding, Ti; Qiao, You Lin; Gao, Yu Tang; Koh, Woon Puay; Xiang, Yong Bing; Tang, Ze Zhong; Fan, Jin Hu; Chung, Charles C.; Wang, Chaoyu; Wheeler, William; Yeager, Meredith; Yuenger, Jeff; Hutchinson, Amy; Jacobs, Kevin B.; Giffen, Carol A.; Burdett, Laurie; Fraumeni, Joseph F.; Tucker, Margaret A.; Chow, Wong Ho; Zhao, Xue Ke; Li, Jiang Man; Li, Ai Li; Sun, Liang Dan; Wei, Wu; Li, Ji Lin; Zhang, Peng; Li, Hong Lei; Cui, Wen Yan; Wang, Wei Peng; Liu, Zhi Cai; Yang, Xia; Fu, Wen Jing; Cui, Ji Li; Lin, Hong Li; Zhu, Wen Liang; Liu, Min; Chen, Xi; Chen, Jie; Guo, Li; Han, Jing Jing; Zhou, Sheng Li; Huang, Jia; Wu, Yue; Yuan, Chao; Huang, Jing; Ji, Ai Fang; Kul, Jian Wei; Fan, Zhong Min; Wang, Jian Po; Zhang, Dong Yun; Zhang, Lian Qun; Zhang, Wei; Chen, Yuan Fang; Ren, Jing Li; Li, Xiu Min; Dong, Jin Cheng; Xing, Guo Lan; Guo, Zhi Gang; Yang, Jian Xue; Mao, Yi Ming; Yuan, Yuan; Guo, Er Tao; Zhang, Wei; Hou, Zhi Chao; Liu, Jing; Li, Yan; Tang, Sa; Chang, Jia; Peng, Xiu Qin; Han, Min; Yin, Wan Li; Liu, Ya Li; Hu, Yan Long; Liu, Yu; Yang, Liu Qin; Zhu, Fu Guo; Yang, Xiu Feng; Feng, Xiao Shan; Wang, Zhou; Li, Yin; Gao, She Gan; Liu, Hai Lin; Yuan, Ling; Jin, Yan; Zhang, Yan Rui; Sheyhidin, Ilyar; Li, Feng; Chen, Bao Ping; Ren, Shu Wei; Liu, Bin; Li, Dan; Zhang, Gao Fu; Yue, Wen Bin; Feng, Chang Wei; Qige, Qirenwang; Zhao, Jian Ting; Yang, Wen Jun; Lei, Guang Yan; Chen, Long Qi; Li, En Min; Xu, Li Yan; Wu, Zhi Yong; Bao, Zhi Qin; Chen, Ji Li; Li, Xian Chang; Zhuang, Xiang; Zhou, Ying Fa; Zuo, Xian Bo; Dong, Zi Ming; Wang, Lu Wen; Fan, Xue Pin; Wang, Jin; Zhou, Qi; Ma, Guo Shun; Zhang, Qin Xian; Liu, Hai; Jian, Xin Ying; Lian, Sin Yong; Wang, Jin Sheng; Chang, Fu Bao; Lu, Chang Dong; Miao, Jian Jun; Chen, Zhi Guo; Wang, Ran; Guo, Ming; Fan, Zeng Lin; Tao, Ping; Liu, Tai Jing; Wei, Jin Chang; Kong, Qing Peng; Fan, Lei; Wang, Xian Zeng; Gao, Fu Sheng; Wang, Tian Yun; Xie, Dong; Wang, Li; Chen, Shu Qing; Yang, Wan Cai; Hong, Jun Yan; Wang, Liang; Qiu, Song Liang; Goldstein, Alisa M.; Yuan, Zhi Qing; Chanock, Stephen J.; Zhang, Xue Jun; Taylor, Philip R.; Wang, Li Dong.

In: Human molecular genetics, Vol. 21, No. 9, dds029, 01.05.2012, p. 2132-2141.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China

T2 - A meta-analysis of genome-wide association studies

AU - Abnet, Christian C.

AU - Wang, Zhaoming

AU - Song, Xin

AU - Hu, Nan

AU - Zhou, Fu You

AU - Freedman, Neal D.

AU - Li, Xue Min

AU - Yu, Kai

AU - Shu, Xiao Ou

AU - Yuan, Jian Min

AU - Zheng, Wei

AU - Dawsey, Sanford M.

AU - Liao, Linda M.

AU - Lee, Maxwell P.

AU - Ding, Ti

AU - Qiao, You Lin

AU - Gao, Yu Tang

AU - Koh, Woon Puay

AU - Xiang, Yong Bing

AU - Tang, Ze Zhong

AU - Fan, Jin Hu

AU - Chung, Charles C.

AU - Wang, Chaoyu

AU - Wheeler, William

AU - Yeager, Meredith

AU - Yuenger, Jeff

AU - Hutchinson, Amy

AU - Jacobs, Kevin B.

AU - Giffen, Carol A.

AU - Burdett, Laurie

AU - Fraumeni, Joseph F.

AU - Tucker, Margaret A.

AU - Chow, Wong Ho

AU - Zhao, Xue Ke

AU - Li, Jiang Man

AU - Li, Ai Li

AU - Sun, Liang Dan

AU - Wei, Wu

AU - Li, Ji Lin

AU - Zhang, Peng

AU - Li, Hong Lei

AU - Cui, Wen Yan

AU - Wang, Wei Peng

AU - Liu, Zhi Cai

AU - Yang, Xia

AU - Fu, Wen Jing

AU - Cui, Ji Li

AU - Lin, Hong Li

AU - Zhu, Wen Liang

AU - Liu, Min

AU - Chen, Xi

AU - Chen, Jie

AU - Guo, Li

AU - Han, Jing Jing

AU - Zhou, Sheng Li

AU - Huang, Jia

AU - Wu, Yue

AU - Yuan, Chao

AU - Huang, Jing

AU - Ji, Ai Fang

AU - Kul, Jian Wei

AU - Fan, Zhong Min

AU - Wang, Jian Po

AU - Zhang, Dong Yun

AU - Zhang, Lian Qun

AU - Zhang, Wei

AU - Chen, Yuan Fang

AU - Ren, Jing Li

AU - Li, Xiu Min

AU - Dong, Jin Cheng

AU - Xing, Guo Lan

AU - Guo, Zhi Gang

AU - Yang, Jian Xue

AU - Mao, Yi Ming

AU - Yuan, Yuan

AU - Guo, Er Tao

AU - Zhang, Wei

AU - Hou, Zhi Chao

AU - Liu, Jing

AU - Li, Yan

AU - Tang, Sa

AU - Chang, Jia

AU - Peng, Xiu Qin

AU - Han, Min

AU - Yin, Wan Li

AU - Liu, Ya Li

AU - Hu, Yan Long

AU - Liu, Yu

AU - Yang, Liu Qin

AU - Zhu, Fu Guo

AU - Yang, Xiu Feng

AU - Feng, Xiao Shan

AU - Wang, Zhou

AU - Li, Yin

AU - Gao, She Gan

AU - Liu, Hai Lin

AU - Yuan, Ling

AU - Jin, Yan

AU - Zhang, Yan Rui

AU - Sheyhidin, Ilyar

AU - Li, Feng

AU - Chen, Bao Ping

AU - Ren, Shu Wei

AU - Liu, Bin

AU - Li, Dan

AU - Zhang, Gao Fu

AU - Yue, Wen Bin

AU - Feng, Chang Wei

AU - Qige, Qirenwang

AU - Zhao, Jian Ting

AU - Yang, Wen Jun

AU - Lei, Guang Yan

AU - Chen, Long Qi

AU - Li, En Min

AU - Xu, Li Yan

AU - Wu, Zhi Yong

AU - Bao, Zhi Qin

AU - Chen, Ji Li

AU - Li, Xian Chang

AU - Zhuang, Xiang

AU - Zhou, Ying Fa

AU - Zuo, Xian Bo

AU - Dong, Zi Ming

AU - Wang, Lu Wen

AU - Fan, Xue Pin

AU - Wang, Jin

AU - Zhou, Qi

AU - Ma, Guo Shun

AU - Zhang, Qin Xian

AU - Liu, Hai

AU - Jian, Xin Ying

AU - Lian, Sin Yong

AU - Wang, Jin Sheng

AU - Chang, Fu Bao

AU - Lu, Chang Dong

AU - Miao, Jian Jun

AU - Chen, Zhi Guo

AU - Wang, Ran

AU - Guo, Ming

AU - Fan, Zeng Lin

AU - Tao, Ping

AU - Liu, Tai Jing

AU - Wei, Jin Chang

AU - Kong, Qing Peng

AU - Fan, Lei

AU - Wang, Xian Zeng

AU - Gao, Fu Sheng

AU - Wang, Tian Yun

AU - Xie, Dong

AU - Wang, Li

AU - Chen, Shu Qing

AU - Yang, Wan Cai

AU - Hong, Jun Yan

AU - Wang, Liang

AU - Qiu, Song Liang

AU - Goldstein, Alisa M.

AU - Yuan, Zhi Qing

AU - Chanock, Stephen J.

AU - Zhang, Xue Jun

AU - Taylor, Philip R.

AU - Wang, Li Dong

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84859258707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859258707&partnerID=8YFLogxK

U2 - 10.1093/hmg/dds029

DO - 10.1093/hmg/dds029

M3 - Article

C2 - 22323360

AN - SCOPUS:84859258707

VL - 21

SP - 2132

EP - 2141

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 9

M1 - dds029

ER -