Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma

• Published in: Nature genetics Vol. 45; no. 1; pp. 72 - 75
• Main Authors: Jiang, De-Ke, Sun, Jielin, Cao, Guangwen, Liu, Yao, Lin, Dongxin, Gao, Yu-Zhen, Ren, Wei-Hua, Long, Xi-Dai, Zhang, Hongxing, Ma, Xiao-Pin, Wang, Zhong, Jiang, Wei, Chen, Tao-Yang, Gao, Yong, Sun, Liang-Dan, Long, Ji-Rong, Huang, Hui-Xing, Wang, Dan, Yu, Hongjie, Zhang, Pengyin, Tang, Li-Sha, Peng, Bo, Cai, Hao, Liu, Ting-Ting, Zhou, Ping, Liu, Fang, Lin, Xiaoling, Tao, Sha, Wan, Bo, Sai-Yin, He-Xi Ge, Qin, Lun-Xiu, Yin, Jianhua, Liu, Li, Wu, Chen, Pei, Yan, Zhou, Yuan-Feng, Zhai, Yun, Lu, Pei-Xin, Tan, Aihua, Zuo, Xian-Bo, Fan, Jia, Chang, Jiang, Gu, Xiaoli, Wang, Neng-Jin, Li, Yang, Liu, Yin-Kun, Zhai, Kan, Zhang, Hongwei, Hu, Zhibin, Liu, Jun, Yi, Qing, Xiang, Yongbing, Shi, Rong, Ding, Qiang, Zheng, Wei, Shu, Xiao-Ou, Mo, Zengnan, Shugart, Yin Yao, Zhang, Xue-Jun, Zhou, Gangqiao, Shen, Hongbing, Zheng, S Lilly, Xu, Jianfeng, Yu, Long
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.01.2013
• Subjects: Autoimmune diseases; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Confidence intervals; Disease susceptibility; Gene Expression; Genes; Genetic engineering; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomes; Genotype; Health aspects; Hepatitis B - complications; Hepatitis B - virology; Hepatitis B virus; Hepatitis B virus - genetics; Hepatoma; HLA-DQ Antigens - genetics; Humans; Life sciences; Liver Neoplasms - complications; Liver Neoplasms - genetics; Liver Neoplasms - virology; Polymorphism, Single Nucleotide; Population; Quality control; Risk factors; Science; Single nucleotide polymorphisms; STAT4 Transcription Factor - genetics; Studies; United States; China; Beijing China
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.2483

To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).