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Nature Genetics | Letter
Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers
* Hongxing Zhang, * Yun Zhai, * Zhibin Hu, * Chen Wu, * Ji Qian, * Weihua Jia,
* Fuchao Ma, * Wenfeng Huang, * Lixia Yu, * Wei Yue, * Zhifu Wang, * Peiyao Li,
* Yang Zhang, * Renxiang Liang, * Zhongliang Wei, * Ying Cui, * Weimin Xie, * Mi Cai,
* Xinsen Yu, * Yunfei Yuan, * Xia Xia, * Xiumei Zhang, * Hao Yang, * Wei Qiu, ] *
Jingmin Yang, * Feng Gong, * Minshan Chen, * Hongbing Shen, * Dongxin Lin, * Yi-Xin Zeng, * Fuchu He * & Gangqiao Zhou * et al.
* Affiliations * Contributions * Corresponding authors
Journal name: Nature Genetics
Year published: (2010)
DOI: doi:10.1038/ng.638
Received 12 February 2010
Accepted 08 July 2010
Published online 01 August 2010
To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1,962 individuals with HCC, 1,430 control subjects and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 × 10−18). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B- or PGD-related pathways might be involved in the pathogenesis of this malignancy.
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1.
These authors contributed equally to this work.
* Zhibin Hu,
* Chen Wu,
* Ji Qian &
* Weihua Jia
Affiliations
1.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
* Hongxing Zhang,
* Yun Zhai,
* Lixia Yu,
* Wei Yue,
* Zhifu Wang,
* Peiyao Li,
* Yang Zhang,
* Mi Cai,
* Xia Xia,
* Xiumei Zhang,
* Hao Yang,
* Wei Qiu,
* Feng Gong,
* Fuchu He &
* Gangqiao Zhou
2.
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
* Zhibin Hu &
* Hongbing Shen
3.
Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing, China.
* Chen Wu &
* Dongxin Lin
4.
MOE Key Laboratory of Contemporary Anthropology and Center for Evolutionary Biology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
* Ji Qian &
* Jingmin Yang
5.
State Key Laboratory of Oncology in Southern China, Guangzhou, Guangdong, China.
* Weihua Jia,
* Yunfei Yuan &
* Yi-Xin Zeng
6.
Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
* Weihua Jia &
* Yi-Xin Zeng
7.
Cancer Institute of Guangxi, Nanning, Guangxi, China.
* Fuchao Ma,
* Wenfeng Huang,
* Ying Cui &
* Weimin Xie
8.
Liver Cancer Institute at Fusui County, Guangxi, China.
* Renxiang Liang &
* Zhongliang Wei
9.
Disease Prevention and Control Center at Haimen County, Jiangsu, China.
* Xinsen Yu
10.
Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
* Minshan Chen
11.
Institute of Biomedical Sciences, Fudan University, Shanghai, China.
* Fuchu He
Contributions
G.Z. and F.H. were the overall GWAS study principal investigators who conceived the study and obtained financial support. F.H., G.Z. and H.Z. designed the study. Y.C., W.X., R.L., Z.W., F.M. and W.H. were responsible for recruitment of Guangxi subjects, phenotype collection and biological sample collection and preparation. W.J., Y.Y., M.C. and Y.-X.Z. were responsible for recruitment of Guangdong subjects, phenotype collection and biological sample collection and preparation. Z.H., H.S. and X.Y. were responsible for recruitment of Jiangsu subjects, phenotype collection and biological sample collection and preparation. J.Y. and J.Q. were responsible for recruitment of Shanghai subjects, phenotype collection and biological sample collection and preparation. C.W. and D.L. were responsible for recruitment of Beijing subjects, phenotype collection and biological sample collection and preparation. Y.Z., L.Y., P.L., Z.W., F.M., W.H., W.Y., M.C., X.Z., W.Q., H.Y. and H.Z. performed genotyping in the replication stage. X.X. helped to manage genotype data. F.G., Y.Z. and F.M. conducted functional experiments. G.Z. and H.Z. conducted sample selection and data management, performed statistical analyses, interpreted results and wrote the manuscript.
Competing financial interests
The authors declare no competing financial interests.
Corresponding authors
Correspondence to:
* Gangqiao Zhou ([email protected]) or
* Fuchu He ([email protected])
Supplementary information
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