Inflammatory Gene Polymorphisms in Lung Cancer Susceptibility

Introduction Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer. Methods A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [ IFNG ], interleukin 10 gene [ IL10 ], interleukin 1 alpha gene [ IL1A ], interleukin 1 beta gene [ IL1B ], interleukin 2 gene [ IL2 ], interleukin 4 receptor gene [ IL4R ], interleukin 4 gene [ IL4 ], interleukin 6 gene [ IL6 ], prostaglandin-endoperoxide synthase 2 gene [ PTGS2 ] (also known as COX2 ), transforming growth factor beta 1 gene [ TGFB1 ], and tumor necrosis factor alpha gene [ TNFA ]) was evaluated. Results Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511 C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58–0.94] and OR = 0.71 [95% CI: 0.50–1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59–0.95] and OR = 0.69 [95% CI: 0.46–1.03], respectively, p = 0.03). Survival was not influenced by genotype. Conclusions This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer.