Single Nucleotide Polymorphisms in TGF-β1 and Their Association with HCC Development in HCV Patients

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with chronic hepatitis C virus (HCV) infection serving as a principal risk factor. Genetic polymorphisms in cytokine genes such as transforming growth factor beta 1 (TGF-β1) may modulate susceptibility to HCC by influencing the hepatic microenvironment and carcinogenic progression. Objective: To investigate the association between the TGF-β1 -509 C/T promoter polymorphism and the risk of HCC among chronic HCV patients in a Pakistani population. Methods: This comparative study enrolled 80 adult patients from Sheikh Zayed Hospital, Lahore, including 40 with chronic HCV infection without HCC and 40 with HCC secondary to chronic HCV. Genomic DNA was extracted from whole blood samples and genotyped for TGF-β1 -509 C/T using PCR-RFLP. Demographic, clinical, and laboratory data were collected, and genotype distributions were compared between groups. Statistical analyses included chi-square testing, odds ratio calculation, and logistic regression to assess associations and control for confounders. Results: The TT genotype and T allele of TGF-β1 -509 were more frequent in HCC patients compared to those with HCV alone. The TT genotype was associated with an increased, but not statistically significant, risk of HCC (OR 2.51; 95% CI 0.79–8.03; p=0.120). Clinical parameters such as tumor size and serum AFP were higher in TT and CT carriers, suggesting a trend toward more aggressive disease. Conclusion: While the TGF-β1 -509 TT genotype and T allele showed higher prevalence and risk estimates in HCC patients with chronic HCV, statistical significance was not reached. These findings suggest a possible genetic contribution to HCC susceptibility in this population, meriting further investigation in larger cohorts.