Association of interleukin 1 beta (IL-1β) polymorphism with mRNA expression and risk of non small cell lung cancer

Meta Gene. 2014 Jan 17:2:123-33. doi: 10.1016/j.mgene.2013.12.002. eCollection 2014 Dec.

Abstract

Introduction: Interleukin 1 beta (IL- 1β), a key proinflammatory cytokine encoded by the interleukin 1 beta gene, has been associated with chronic inflammation and plays an important role in lung inflammatory diseases including lung cancer. Elevated levels of Interleukin 1proteins, in particular interleukin 1 beta greatly enhance the intensity of the inflammatory response.

Aim: To study the role of interleukin 1 beta-31C > T and -511 T > C polymorphism in the pathogenesis of non small cell lung cancer (NSCLC).

Materials and methods: One hundred and ninety non small cell lung cancer patients and 200 healthy age, sex, smoking and dwelling matched controls were used for polymorphic analysis by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. Normal tissues of 48 histopathologically confirmed non small cell lung cancer patients were taken for mRNA expression analysis. Quantitation of interleukin 1 beta was carried out by quantitative real time PCR.

Result: The T/T genotype of interleukin 1 beta-31 gene was significantly associated with increased risk of NSCLC [(P = 0.001, OR - 2.8 (95%CI 1.52-5.26)]. The interleukin 1 beta - 511 T > C does not show any difference between the NSCLC and control group (P = 0.3, OR - 0.72 (95%CI 0.41-1.28). Quantitative analysis of mRNA showed significant association with interleukin 1 beta T allele as compared to the interleukin 1 beta-31C allele (P = 0.006).

Conclusion: We conclude that lung cancer risk genotype interleukin 1 beta-31TT results in increased expression of interleukin 1 beta mRNA in lung cancer patients. Our data suggest that this genotype (IL1β -31TT) in the interleukin 1 beta regulatory region provide a microenvironment with elevated inflammatory stimuli and thus increasing the risk for lung cancer.

Keywords: Inflammation; Non small cell lung cancer; Polymorphism; Restriction fragment length polymorphism (RFLP).