title: Expression quantitative trait loci for TNFRSF10 influence both HBV infection and hepatocellular carcinoma development.
abstract: Tumor necrosis factor receptor superfamily member 10 (TNFRSF10) is a death domain-containing receptor for the apoptotic ligand TNFSF10, which involves multiple processes, including hepatocarcinogenesis and immune response against HBV infection. Several single nucleotide polymorphisms (SNPs) were identified as expression quantitative trait loci (eQTLs) for TNFRSF10. To assess the association of TNFRSF10 eQTL SNPs with the risk of hepatocellular carcinoma (HCC) and chronic HBV infection, we designed a case-control study that included 1,300 HBV-related HCC patients, 1,344 chronic HBV carriers, and 1,344 subjects with HBV natural clearance, and then genotyped two TNFRSF10 eQTL SNPs (rs79037040 and rs2055822). We found that rs79037040 GT/TT genotypes were associated with a decreased HCC risk (adjusted odds ratio [OR] = 0.83, 95% confidence intervals [CIs] = 0.71-0.97, P = 0.021) but an increased chronic HBV infection risk of borderline significance (adjusted OR = 1.14, 95%CIs = 0.98-1.33, P = 0.085). In contrast, the rs2055822 G allele was a risk factor for HCC (adjusted OR = 1.12, 95%CIs = 1.00-1.25, P = 0.041) but a protective factor for chronic HBV infection (adjusted OR = 0.89, 95%CIs = 0.80-0.99, P = 0.038). Furthermore, we observed a dose-dependent relationship between the number of alleles (rs79037040-T and rs2055822-A) and the risk of HCC and chronic HBV infection. In comparison with "0" alleles, having "1-4" alleles was significantly associated with decreased HCC risk and increased HBV infection risk. These findings suggest that eQTL SNPs for TNFRSF10 may be susceptibility markers for HCC and chronic HBV infection.
authors: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Juan
authors: J
authors: Wen
authors: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Ci
authors: C
authors: Song
authors: Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
authors: Jibin
authors: J
authors: Liu
authors: Qidong Liver Cancer Institute, Qidong, China.
authors: Jianguo
authors: J
authors: Chen
authors: Department of Infection Diseases, Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
authors: Xiangjun
authors: X
authors: Zhai
authors: Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Zhibin
authors: Z
authors: Hu
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D012307:Risk Factors
chemical_list: D005819:Genetic Markers; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human
keywords: HBV; HCC; TNFRSF10; eQTLs; lncRNA