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.