Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer

IL-1 receptor antagonist (IL-1ra), a structural variant of IL-1, binds to the same IL-1 receptor and acts as a competitive inhibitor of IL-1 bioactivity. IL-1ra protein has been widely investigated and found to be associated with different human malignancies. In the second intron of the IL-1RN gene, there is a functional polymorphism of a variable number of tandem repeats (VNTR), which is characterized as having an importance role in regulating the serum IL-1ra levels, human immune response and cancer risk. We genotyped this VNTR of IL-1RN in a case-control study of 885 histologically confirmed lung cancer patients and 1024 cancer-free controls frequency-matched to the cases on age and sex in a Chinese population to evaluate the association of this variant and lung cancer risk. We found that the presence of the allele 2 of IL-1RN(IL-RN*2) was associated with a 32% significantly decreased risk of lung cancer (adjusted OR, 0.68; 95% CI, 0.52-0.89). Stratified analyses revealed that the reduced risks associated with the genotypes with IL-RN*2 allele (I/II and II/II) were more evident in nonsmokers (adjusted OR, 0.53; 95% CI, 0.35-0.79) and in subjects with squamous cell carcinoma (adjusted OR, 0.49; 95% CI, 0.31-0.76). These findings support our priori hypothesis that the IL1RN*2 allele may contribute to lung cancer risk in the Chinese population. More functional data for this IL1RN polymorphism are warranted to explore its role in lung carcinogenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.