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

Cancer Lett. 2006 May 18;236(2):269-75. doi: 10.1016/j.canlet.2005.05.015. Epub 2005 Jul 14.


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*2allele (I/II and II/II) were more evident in non-smokers (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Aged
  • Carcinoma, Large Cell / genetics*
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • China
  • Female
  • Gene Frequency*
  • Genotype
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Introns
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Minisatellite Repeats
  • Polymorphism, Genetic
  • Risk Factors
  • Sialoglycoproteins / genetics*
  • Smoking / genetics


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Sialoglycoproteins