Interleukin 1 receptor antagonist gene polymorphism and risk of lung cancer: A possible interaction with polymorphisms in the interleukin 1 beta gene

Tobacco smoking is the main risk factor for lung cancer. Only 10-15% of smokers develop lung cancer, suggesting that genetic factors are of importance in determining individual susceptibility to the disease. Several studies in recent years indicate that chronic inflammation is a cofactor in lung carcinogenesis. We have previously reported an association of interteukin 1 beta gene (IL1B) potymorphisms with lung cancer risk. Interleukin-1 receptor antagonist (IL-1 Ra) has been implicated in carcinogenesis of different cancer types. IL- 1 Ra binds competitively to the same membrane receptor as interteukin-1 beta (IL-1 beta) and thereby acts as an antagonist to the pro-inflammatory actions of IL-1 P. The aim of the study was to examine whether a common VNTR polymorphism in the interleukin 1 receptor antagonist gene (IL1RN) is associated with lung cancer risk. Due to the tight relationship between IL1RN and IL1B, we also explored the possibility of an interaction between the two genes. The study population comprised of 340 non-small cell lung cancer cases and 412 healthy controls of Norwegian origin. Our results indicate that individuals homozygous for the lL1RN*1 allele and carrying the IL1B-31T allete had increased risk of non-small cell lung cancer (odds ratio C/T 3.08; 1.10-8.62 and T/T 5.87; 2.15-16.05). Furthermore, IL1RN*1 carriers had nearly two-fold higher levels of bulky/hydrophobic DNA adducts in the lung. Our findings support the significance of 10 gene cluster polymorphisms and risk of lung cancer. (c) 2005 Elsevier Ireland Ltd. All rights reserved.