title: Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma.
abstract: 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)).
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: De-Ke
authors.initials: DK
authors.lastname: Jiang
authors.forename: Jielin
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authors.lastname: Sun
authors.forename: Guangwen
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authors.lastname: Cao
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authors.forename: Dongxin
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authors.lastname: Wang
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authors.lastname: Jiang
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authors.lastname: Gao
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authors.lastname: Long
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authors.lastname: Huang
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authors.lastname: Wang
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authors.lastname: Yu
authors.forename: Pengyin
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authors.lastname: Zhang
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authors.lastname: Peng
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authors.lastname: Zhou
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authors.lastname: Lin
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authors.lastname: Tao
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authors.lastname: Wan
authors.forename: He-Xi Ge
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authors.lastname: Sai-Yin
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authors.lastname: Qin
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authors.lastname: Yin
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authors.lastname: Liu
authors.forename: Chen
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authors.lastname: Wu
authors.forename: Yan
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authors.lastname: Pei
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Zhou
authors.forename: Yun
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authors.lastname: Zhai
authors.forename: Pei-Xin
authors.initials: PX
authors.lastname: Lu
authors.forename: Aihua
authors.initials: A
authors.lastname: Tan
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gu
authors.forename: Neng-Jin
authors.initials: NJ
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yin-Kun
authors.initials: YK
authors.lastname: Liu
authors.forename: Kan
authors.initials: K
authors.lastname: Zhai
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Yi
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Xiang
authors.forename: Rong
authors.initials: R
authors.lastname: Shi
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
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authors.initials: SL
authors.lastname: Zheng
authors.forename: Jianfeng
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authors.lastname: Xu
authors.forename: Long
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authors.lastname: Yu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000235:genetics* / Q000821:virology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006509:Hepatitis B / Q000150:complications* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications* / Q000235:genetics* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D050797:STAT4 Transcription Factor / Q000235:genetics*
chemical_list: D006683:HLA-DQ Antigens; D050797:STAT4 Transcription Factor