Association of the GLB1 rs4678680 genetic variant with risk of HBV-related hepatocellular carcinoma.

// Wen-Tao Wang 1, * , Ziqiang Li 1, * , Meng Shi 2, 3 , Hui Zhu 4 , Xiangyu Xiong 3 , Jinhua Shang 3 , Jibing Liu 5 , Mujian Teng 1 , Ming Yang 2 1 Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, China 2 Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China 3 College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China 4 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China 5 Department of Intervention Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China * These authors contributed equally to this work Correspondence to: Ming Yang, email: aaryoung@yeah.net Keywords: GLB1, genetic polymorphism, HBV, HCC, susceptibility Received: June 13, 2016      Accepted: July 19, 2016      Published: July 30, 2016 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.