Abstract 921: Polymorphisms in inflammatory pathway genes, host factors, and lung cancer risk in non-smoking Chinese women

Introduction Current evidence suggests that inflammation plays an important role in lung carcinogenesis in smokers, but its effect in non-smokers is still unclear. Previous studies have reported increased lung cancer risk with past history of lung disease such as tuberculosis and asthma, and with polymorphisms of genes in the inflammatory pathway. We examined the effect of self-reported chronic lung disease and allergic conditions and 6 polymorphisms in key inflammatory genes on lung cancer risk in a group of non-smoking Chinese women. Methods 434 never-smoker primary lung cancer cases and 1375 controls were recruited from 4 major hospitals in Singapore in 2 case-control studies (conducted 1996-8 and 2005-8) using similar methods and questionnaires. Data on relevant exposures were obtained by in-hospital face-to-face interviews. 6 polymorphisms in the interleukin 1-β (IL1-β), interleukin-6 (IL6), cyclooxygenase-2 (COX2), Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ), and interleukin-1β receptor antagonist (IL1-βRa) genes were genotyped. Results A previous history of chronic lung disease (TB/chronic bronchitis or emphysema) increased the risk of lung cancer (Adjusted OR 1.33, 95%CI 1.06-1.66). This increased risk was not modified by the inflammatory genotypes studied. We noticed a main effect on lung cancer of polymorphism in the 1L6 gene, a pro-inflammatory cytokine present in high levels in lung tumour tissue, but not in the other polymorphisms studied. The C/G or G/G genotype at the IL6-634C/G Single Nucleotide Polymorphism (SNP) site (which has been shown to increase the production and secretion of IL6) was associated with an increased risk of lung cancer (OR 1.37, 95%CI 1.02-1.82) compared to the C/C genotype. While a history of asthma/atopy alone did not enhance risk (OR 0.98, 95%CI 0.75-1.27), interactions were observed between hypersensitivity and polymorphisms in 2 inflammatory pathway genes. A history of asthma/atopy and the presence of the T/T genotype at IL1-β-31T/C SNP site conferred a risk of 2.31 (95%CI 1.26-4.24, Likelihood Ratio [LR] test for interaction p = 0.016), compared to no asthma/atopy and a C/C genotype. A history of asthma/atopy and the presence of either *1/*2 or *2/*2 genotypes of the IL1-bRa gene was associated with a risk of 2.81 (95%CI 1.18-6.71, LR test p = 0.034) compared to no asthma/atopy and the *1/*1 genotype. In both cases, the increased risk associated with asthma/atopy was restricted only to those individuals with the at-risk genotypes. Conclusion These findings are consistent with the hypothesis that chronic inflammation plays a role in lung cancer development in non-smoking Asian women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 921.