Role of IL-4 Gene Polymorphisms in HBV-Related Hepatocellular Carcinoma in a Chinese Population

Background: Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association. Objectives: To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, -590C/T (rs2243250) and -33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population. Methods: IL-4 -590C/T and -33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. Results: Overall, no significant differences were observed regarding the IL-4 -590C/T and -33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 -590C/T and -33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094-16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032-11.458, P = 0.044) and CC versus TT+ CT (OR: 4.09, 95% CI: 1.08-15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04-11.28, P = 0.042)]. Conclusions: These findings suggest that genetic variants in IL-4 -590C/T and -33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.