title: 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.
authors.affiliation: Molecular Oncology Group - CI, Portuguese Institute of Oncology, Porto, Portugal. monicagomes26@gmail.com
authors.forename: Mónica
authors.initials: M
authors.lastname: Gomes
authors.forename: Ana
authors.initials: A
authors.lastname: Coelho
authors.forename: António
authors.initials: A
authors.lastname: Araújo
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Teixeira
authors.forename: Raquel
authors.initials: R
authors.lastname: Catarino
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D015847:Interleukin-4