Interleukin-18 promoter polymorphism is associated with lung cancer: a case-control study

Interleukin-18 (IL-18) is a multifunctional cytokine that augments IFN-gamma production and affects tumor immune response. In the present case-control study, we tested whether IL-18 promoter polymorphism contributes to lung cancer susceptibility in Iranian patients.

The study groups were 73 patients with lung cancer, including 53 with squamous carcinoma (SC) and 20 with small cell lung carcinoma (SCLC), and 97 healthy regional aged-matched individuals. The frequency of IL-18 promoter single nucleotide polymorphisms (SNPs) at positions -656 (G/T), -607 (C/A), and -137 (G/C) was determined by polymerase chain reaction analyses.

There were significant differences in the IL-18 -607 allele and genotype distributions between the 73 lung cancer patients and controls. A significantly higher A allele frequency at position -607, which is associated with lower IL-18 production, was observed in lung cancer patients (48.6% vs. 35%; OR = 1.75; 95% CI 1.13-2.72). Also, patients with the -607 CA and the AA genotypes had a 2.60-fold (95% CI 1.26-5.36) and 3.15-fold (95% CI 1.16-8.55) increase in risk of lung cancer. Subdivision of the patients according to histological type revealed that SC was significantly associated with IL-18 -607 SNPs. Although the percentages of -607 alleles and genotypes in SCLC patients were similar to the results in SC patients, the differences compared to control individuals did not reach statistical significance. Analysis with Arlequin software identified eight haplotypes from three SNPs analyzed here. The distributions of IL-18 gene haplotypes were not significantly different between patients and controls after Bonferroni correction.

This is the first report to investigate the association between IL-18 polymorphism and lung cancer. Our results suggest that IL-18 polymorphism contributes to the lung cancer risk, particularly among SC patients. Further studies with larger numbers of patients are required to determine the possible association between IL-18 polymorphisms and different histological types of lung cancer.