title: Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers.
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.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Chen
authors.initials: C
authors.lastname: Wu
authors.forename: Ji
authors.initials: J
authors.lastname: Qian
authors.forename: Weihua
authors.initials: W
authors.lastname: Jia
authors.forename: Fuchao
authors.initials: F
authors.lastname: Ma
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Huang
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Yue
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Wang
authors.forename: Peiyao
authors.initials: P
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Renxiang
authors.initials: R
authors.lastname: Liang
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Wei
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Weimin
authors.initials: W
authors.lastname: Xie
authors.forename: Mi
authors.initials: M
authors.lastname: Cai
authors.forename: Xinsen
authors.initials: X
authors.lastname: Yu
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xia
authors.initials: X
authors.lastname: Xia
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.forename: Jingmin
authors.initials: J
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Gong
authors.forename: Minshan
authors.initials: M
authors.lastname: Chen
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics*; D002353:Carrier State / Q000473:pathology; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide