IL-2 polymorphisms and IL-2 serum levels association with susceptibility to HBV-related Hepatocellular Carcinoma

Polymorphisms in cytokine genes responsible for inflammatory and immune responses are associated with risk of hepatocellular carcinoma (HCC) in high-risk population. Interleukin-2 (IL-2) is an immuno-regulatory cytokine produced by T cells and plays an important role in anti-tumor immunity. Variations in the DNA sequence of the IL-2 gene may lead to altered cytokine production and/or activity, and thus modulate an individual’s susceptibility to hepatitis B virus-related hepato-cellular carcinoma (HBV-related HCC). Aim: This study aimed to investigate whether IL-2 gene polymorphisms and its serum levels are associated with HBV-related HCC. Patients and Methods: The -384 T/G polymorphisms in the IL-2 gene were examined in 25 cases of chronic hepatitis B (CHB), 25 cases of HBV-related liver cirrhosis (LC), 25 cases of HBV-related HCC, and 25 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The serum IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: The results showed that there were highly significant difference between HBV-related HCC patients and healthy controls regarding the genotype and allele frequencies of the IL-2 polymorphisms respectively. The TG (OR = 4.81, 95% CI, 1.14 – 20.25, P = 0.03) and GG (OR = 11.67, 95% CI, 2.13 – 64.04, P = 0.003) genotypes were correlated with a significant increased HCC risk as compared with the TT genotype and the G allele was correlated with a significant increased HCC risk when compared with the T allele (OR = 4.2, 95% CI, 1.81 – 9.73, P = 0.001). There was significant decrease in serum IL2 levels between HBV-related HCC patients (177.78±71.7) and healthy controls (256.9±33.2). The genotypes of the IL-2 gene polymorphism were observed significantly correlated with serum IL-2 levels in HBV-related HCC patients with highly significant decrease in serum IL-2 levels in individuals with homozygous GG genotypes (107.7±.8 ng/L) or heterozygous TG genotypes (194.8±12.5 ng/L) than homozygous TT genotypes (306.3±29.8 ng/L) Conclusion: The results suggested that the IL-2 -384 T/G polymorphism might contribute to an increased risk of developing HBV-related HCC by affecting the serum IL-2 secretion. [Ahmed A Sonbol, Blal A Montaser, Hosam El-Din M Seleem. IL-2 polymorphisms and IL-2 serum levels association with susceptibility to HBV-related Hepatocellular Carcinoma. J Am Sci 2015;11(12):116-123]. (ISSN: 1545-1003). http://www.jofamericanscience.org. 16. doi:10.7537/marsjas111215.16.