Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers

被引：279

作者：

Zhang, Hongxing ^{[1
]}

Zhai, Yun ^{[1
]}

Hu, Zhibin ^{[2
]}

Wu, Chen ^{[3
]}

Qian, Ji ^{[4
,5
,6
]}

Jia, Weihua ^{[7
,8
]}

Ma, Fuchao ^{[9
]}

Huang, Wenfeng ^{[9
]}

Yu, Lixia ^{[1
]}

Yue, Wei ^{[1
]}

Wang, Zhifu ^{[1
]}

Li, Peiyao ^{[1
]}

Zhang, Yang ^{[1
]}

Liang, Renxiang ^{[10
]}

Wei, Zhongliang ^{[10
]}

Cui, Ying ^{[9
]}

Xie, Weimin ^{[9
]}

Cai, Mi ^{[1
]}

Yu, Xinsen

Yuan, Yunfei ^{[7
]}

Xia, Xia ^{[1
]}

Zhang, Xiumei ^{[1
]}

Yang, Hao ^{[1
]}

Qiu, Wei ^{[1
]}

Yang, Jingmin ^{[4
,5
,6
]}

Gong, Feng ^{[1
]}

Chen, Minshan ^{[11
]}

Shen, Hongbing ^{[2
]}

Lin, Dongxin ^{[3
]}

Zeng, Yi-Xin ^{[7
,8
]}

He, Fuchu ^{[1
,12
]}

Zhou, Gangqiao ^{[1
]}

机构：

[1] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing, Peoples R China

[2] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China

[3] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100037, Peoples R China

[4] Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China

[5] Fudan Univ, Ctr Evolutionary Biol, Sch Life Sci, Shanghai 200433, Peoples R China

[6] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China

[7] State Key Lab Oncol So China, Guangzhou, Guangdong, Peoples R China

[8] Sun Yat Sen Univ, Ctr Canc, Dept Expt Res, Guangzhou 510275, Guangdong, Peoples R China

[9] Canc Inst Guangxi, Nanning, Guangxi, Peoples R China

[10] Liver Canc Inst Fusui Cty, Guangxi, Peoples R China

[11] Sun Yat Sen Univ, Ctr Canc, Dept Hepatobiliary Oncol, Guangzhou 510275, Guangdong, Peoples R China

[12] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China

来源：

NATURE GENETICS | 2010年 / 42卷 / 09期

关键词：

TUMOR-SUPPRESSOR; CHROMOSOME; 1P; GENE; UBIQUITIN; CANCER; KIF1B; HEPATOCARCINOGENESIS; NEUROBLASTOMA; MUTATION; RISK;

D O I：

10.1038/ng.638

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 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.

引用

页码：755 / U39

页数：5

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