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

• Published in: Nature genetics Vol. 42; no. 9; pp. 755 - 758
• Main Authors: Zhang, Hongxing, Zhai, Yun, Hu, Zhibin, Wu, Chen, Qian, Ji, Jia, Weihua, Ma, Fuchao, Huang, Wenfeng, Yu, Lixia, Yue, Wei, Wang, Zhifu, Li, Peiyao, Zhang, Yang, Liang, Renxiang, Wei, Zhongliang, Cui, Ying, Xie, Weimin, Cai, Mi, Yu, Xinsen, Yuan, Yunfei, Xia, Xia, Zhang, Xiumei, Yang, Hao, Qiu, Wei, Yang, Jingmin, Gong, Feng, Chen, Minshan, Shen, Hongbing, Lin, Dongxin, Zeng, Yi-Xin, He, Fuchu, Zhou, Gangqiao
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2010; Nature Publishing Group
• Subjects: 631/208/205/2138; 631/208/727/2000; 631/326/596/1550; 692/699/1503/1607/1610; Adult; Aged; Agriculture; Animal Genetics and Genomics; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - genetics; Carrier State - pathology; Case-Control Studies; Chromosomes, Human, Pair 1 - genetics; Diagnosis; Disease susceptibility; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene Function; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Health aspects; Hepatitis B virus; Hepatitis B virus - isolation & purification; Hepatitis B, Chronic - complications; Hepatitis B, Chronic - genetics; Hepatoma; Human Genetics; Human viral diseases; Humans; Infectious diseases; letter; Liver Neoplasms - complications; Liver Neoplasms - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; Risk factors; Tumors; Viral diseases; Viral hepatitis; China; Digestive system; Liver; Orthohepadnavirus; Hepatic disease; Hepatocellular carcinoma; Identification; Malignant tumor; Infection; Virus; Viral hepatitis B; Sensitivity; Association; Hepadnaviridae; Viral disease; Susceptibility locus; Digestive diseases; Carrier; Hepatitis B virus; Cancer
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.638

Gangqiao Zhou and colleagues report a genome-wide association study for hepatocellular carcinoma in chronic hepatitis B virus carriers, identifying a new susceptibility locus at chromosome 1p36.22. 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.