Abstract
Accumulated evidences demonstrated that GLB1 is involved in cell senescence and cancer development. The GLB1 rs4678680 single nucleotide polymorphism (SNP) has been identified as a hepatocellular carcinoma (HCC) susceptibility polymorphism by a genome-wide association study in Korean population previously. However, little or nothing was known about its involvement and functional significance in hepatitis B viruses (HBV)-related HCC in Chinese. Therefore, we investigated the association between the GLB1 rs4678680 SNP and HBV-related HCC risk as well as its biological function in vivo. Genotypes were determined in two independent case-control sets from two medical centers of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The potential regulation role the rs4678680 genetic variant on GLB1 expression was examined with HCC and normal liver tissues. We found that The rs4678680 G allele was showed to be risk allele; individuals with the TG genotype had an OR of 1.51 (95% CI = 1.10–2.07, P = 0.010, Shandong set) or 1.49 (95% CI = 1.11–1.99, P = 0.008, Jiangsu set) for developing HBV-related HCC, respectively, compared with individuals with the TT genotype. This association was more pronounced in males, individuals aged older than 57 years and drinkers (all P < 0.05). In the genotype-phenotype correlation analyses of fifty-six human liver tissue samples, rs4678680 TG or GG was associated with a statistically significant increase of GLB1 mRNA expression (P < 0.05). Our data indicated that the GLB1 rs4678680 SNP contributes to susceptibility to develop HBV-related HCC, highlighting the involvement of GLB1 and cell senescence in etiology of HCC.
Highlights
Ranking the fifth most common cancer, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide [1]
It was found that carriers of the rs4678680 TG or GG genotype showed significantly and consistently increased risk to develop hepatitis B viruses (HBV)-related HCC compared with the TT carriers in both case-control sets (Shandong set: Odds ratios (ORs) = 1.53, 95% confidence intervals (CIs) = 1.12–2.10, P = 0.007; Jiangsu set: OR = 1.57, 95% CI = 1.18–2.09, P = 0.002)
We examined the association between the GLB1 rs4678680 single nucleotide polymorphism (SNP) and risk of developing HBV-related HCC in a case-control design
Summary
Ranking the fifth most common cancer, hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide [1]. Since about 75% cases of HCC are associated with HBV infection in China [4], HBV infection is considered as one major risk factor for HCC. Only 15% chronic HBV carriers suffer from HCC in their lifetime [2, 3], indicating that host genetic factors may be involved in development of HBV-related HCC. This notion has been proved by several candidate gene and genome-wide association study (GWAS) on HBV-related HCC in eastern Asians [5,6,7,8,9,10]
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