Abstract
Recent genome-wide associated studies (GWASs) have revealed several common loci associated with the risk of hepatitis B virus (HBV)- or hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We selected 15 single nucleotide polymorphisms (SNPs) identified through GWASs on HBV- or HCV-related HCC, and genotyped them in two independent Chinese cohorts of chronic HBV carriers, including 712 LC cases and 2601 controls. The association of each SNP with the risk of HBV-related LC was assessed by meta-analysis of the two cohorts. Of the 12 SNPs reported in HBV-related HCC GWASs, five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA-DQ), were found to be significantly associated with the risk of HBV-related LC (rs7574865: P = 1.79 × 10−2, OR = 1.17, 95% CI = 1.03–1.34; rs9267673: P = 4.91 × 10−4, OR = 1.37, 95% CI = 1.15–1.63; rs2647073: P = 3.53 × 10−5, OR = 1.63, 95% CI = 1.29–2.06; rs3997872: P = 4.22 × 10−4, OR = 1.86, 95% CI = 1.32–2.62; rs9275319: P = 1.30 × 10−2, OR = 1.32, 95% CI = 1.06–1.64). However, among the three SNPs associated with the risk of HCV-related HCC in previous GWASs, none of them showed significant association with the risk of HBV-related LC. Our results suggested that genetic variants associated with HBV-related hepatocarcinogenesis may already play an important role in the progression from CHB to LC.
Highlights
Hepatitis B virus (HBV) infection is one of the most serious and prevalent health problems worldwide, with endemic areas in Sub-Saharan Africa and Southeast Asia, especially China[1]
In the course of persistent HBV infection, inflammation forms the pathogenetic basis of chronic hepatitis B (CHB) that can lead to nodular fibrosis, which can sequentially progress to liver cirrhosis (LC) and, eventually, hepatocellular carcinoma (HCC)[1,2]
Two genome-wide associated studies (GWASs) on hepatitis C virus (HCV)-related HCC have been carried out and revealed several genetic variants associated with the risk of HCV-related HCC, but they did not report if these variants are involved in the course of HBV induced diseases[15,16]
Summary
Hepatitis B virus (HBV) infection is one of the most serious and prevalent health problems worldwide, with endemic areas in Sub-Saharan Africa and Southeast Asia, especially China[1]. There have been several GWASs on HBV-related HCC9–13, including one GWAS by our group[13] Most of these studies focused on HCC at one time point, which might encompass the progression from CHB to LC14, and did not address the question of whether these genetic factors are involved in the progress from CHB to HBV-related LC. Two GWASs on hepatitis C virus (HCV)-related HCC have been carried out and revealed several genetic variants associated with the risk of HCV-related HCC, but they did not report if these variants are involved in the course of HBV induced diseases[15,16]. We investigated the associations of genetic variants discovered by HBV- and HCV-related HCC GWASs with the risk of the progression from CHB to LC in Chinese population
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