FC25 IL-18 promoter variations at position -607 C/A is associated with individuals susceptibility to Basal Cell Carcinoma

Abstract

Introduction Human keratinocytes are the main source of pro-IL-18. These cells are capable of producing biologically active form of the cytokine. Objectives IL-18 potentially induces IFN-γ production in response to a variety of stimuli and subsequently plays a role in numerous types of skin disorders by promoting inflammation as well as deviation from Th2 to Th1 response. IL-18 and Th1 cytokines have a duel effect against and, simultaneously, in favor of cancer progression. A ‘C to A transition’ at position -607 in IL-18 gene has been recently reported to affect activity of the gene promoter. Aims We aimed to evaluate association of IL-18 gene promoter polymorphism at position -607 C/A with genetic susceptibility to BCC. Methods 97 patients with BCC and 194 matched healthy individuals with no history of cancer or autoimmune disease (mean age: 59.96±10.73) recruited to the study. PCR with Allele specific primer (ASP) was performed to determine genotypes. Results The frequencies of CC, CA and AA genotype in patients and control group were respectively 25.8% vs 38.6%, 60.8% vs 45.4% and 13.4% vs 16%. Statistical analysis revealed that CC genotype frequency in patients was significantly higher than controls (P=0.04, OR=1.82, 95% CI for OR 1.02–3.23). No significant differences was observed in the frequencies of the alleles between two groups (P=0.29). Conclusion Our data suggest that significant increase in CC genotype at locus -607C/A in IL-18 gene is associated with susceptibility to BCC in Iranian population, most likely by promoting IL-18 production at the tumor microenvironment. Key Words: Basal Cell Carcinoma, Interlukin-18, Polymerase Chain Reaction (PCR), Polymorphism