Journal
NATURE GENETICS
Volume 45, Issue 1, Pages 72-U105Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2483
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Funding
- National Natural Science Foundation of China for Creative Research Groups [30024001]
- National Key Sci-Tech Special Project of China [2013ZX10002010, 2008ZX10002-020]
- Shanghai Municipal Science and Technology Commission
- National Natural Science Foundation of China [31071193, 31100895, 30800946]
- Director Foundation of the State Key Laboratory of Genetic Engineering
- Fund from X.-J. Qu and Chang-An Capital of Beijing
- Fund from S.-J. Yan and Tianying S. T. Group of Jiangsu
- MOE Foundation of Cheung Kong Scholars Program
- Huashan Hospital, Fudan University
- Fudan-VARI Center for Genetic Epidemiology, Fudan University
- Foundation for the Author of National Excellent Doctoral Dissertation [201081]
- Program for New Century Excellent Talents in University [NCET-10-0178]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- NATIONAL CANCER INSTITUTE [R01CA082729, R37CA070867] Funding Source: NIH RePORTER
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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 x 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P-meta = 2.72 x 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 x 10(-14)).
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