Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers.
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.
Zhang
Hongxing
H
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
Zhai
Yun
Y
Hu
Zhibin
Z
Wu
Chen
C
Qian
Ji
J
Jia
Weihua
W
Ma
Fuchao
F
Huang
Wenfeng
W
Yu
Lixia
L
Yue
Wei
W
Wang
Zhifu
Z
Li
Peiyao
P
Zhang
Yang
Y
Liang
Renxiang
R
Wei
Zhongliang
Z
Cui
Ying
Y
Xie
Weimin
W
Cai
Mi
M
Yu
Xinsen
X
Yuan
Yunfei
Y
Xia
Xia
X
Zhang
Xiumei
X
Yang
Hao
H
Qiu
Wei
W
Yang
Jingmin
J
Gong
Feng
F
Chen
Minshan
M
Shen
Hongbing
H
Lin
Dongxin
D
Zeng
Yi-Xin
YX
He
Fuchu
F
Zhou
Gangqiao
G
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