Genome-wide Association Study Identifies 1p36.22 As a New Susceptibility Locus for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 Aug 3

PMID 20676096

Citations 165

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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