Influence of functional genetic polymorphism (− 590C/T) in non-small cell lung cancer (NSCLC) development: The paradoxal role of IL-4

Abstract

Lung cancer is the leading cause of death by cancer in the world, originating about 17.5% of total deaths from cancer (1.18 million). Inflammation plays an important role in the pathogenesis of lung cancer. IL-4 is an anti-inflammatory cytokine, which reduces the production of proinflammatory cytokines by monocytes and with direct antiproliferative effects in some tumors. The polymorphism −590C/T SNP is a C to T transition in the −590 position of the promoter region of the IL-4 gene. The aim of this study was to evaluate the influence of this polymorphism in the susceptibility to NSCLC.DNA was extracted from peripheral blood of 1060 individuals (391 patients diagnosed with NSCLC and a control group of 669 individuals without cancer). The characterization of IL-4 −590C/T genotypes was performed by PCR-RFLP (BsmFI).The −590C/T polymorphism genotypes were classified as low (CC) and high expression (TT).The frequencies obtained for the CC and TT genotypes were 90.1% and 9.9%, respectively, in the control group and 92.9% and 7.1%, respectively, in the case group. The analysis of the TT and CC genotype frequencies in the two groups showed a statistically significant difference in its distribution, indicating a protection of 80% for the development of NSCLC, type epidermoid in individuals with the TT genotype when compared with individuals with CC genotype (P=0.024, OR=0.221: 95% CI=0.053–0.928).We present for the first time that increased expression of IL-4 associated with the TT genotype may contribute to immune surveillance during NSCLC development.