Polymorphisms of the interleukin-1 beta gene are associated with increased risk of non-small cell lung cancer.

Lung cancer is one of the leading causes of cancer death worldwide. Tobacco smoking is the main risk factor for lung cancer. Less than 20% of smokers develop lung cancer in their lifetime, however, indicating individual variations in lung cancer risk. Pro-inflammatory cytokines produced by inflammatory cells have been associated with inflammatory diseases and cancer. The IL1B gene, encoding IL-1beta cytokine, contains several single nucleotide polymorphisms (SNPs). Two of these are in the promoter region, at positions -511 (C-T) and -31 (T-C). These polymorphisms have been associated with increased risk of developing a number of inflammatory diseases and gastric carcinoma. We genotyped the 2 polymorphisms in 251 non-small cell lung cancer patients from Norway and 272 healthy controls chosen from the general Norwegian population. The T allele at the -31 SNP (p = 0.01) and C allele at -511 SNP (p < 0.01) were over represented in lung cancer cases. The homozygote subjects were particularly at higher risk of lung cancer with odds ratio of 2.39 (95% CI = 1.29-4.44) for -31T/T and 2.51 (95% CI = 1.47-4.58) for -511C/C genotypes. In view of the significance of the p53 gene in lung carcinogenesis, we also analyzed the IL1B genotypes in relation to p53 mutations in the tumors. The results indicated that subjects having homozygote genotypes were more likely to have a mutation in the p53 gene (p = 0.05). This is the first study to provide evidence for an association of 1L1B gene polymorphisms with lung cancer risk.