Genetic Variation in Innate Immunity and Inflammation Pathways Associated With Lung Cancer Risk

BACKGROUND: Pulmonary inflammation may contribute to lung cancer etiology. The authors conducted a broad evaluation of the association of single nucleotide polymorphisms (SNPs) in innate immunity and inflammation pathways with lung cancer risk and conducted comparisons with a lung cancer genome-wide association study (GWAS). METHODS: In total, 378 patients with lung cancer (cases) and a group of 450 controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were included. A proprietary oligonucleotide pool assay was used to genotype 1429 SNPs. Odds ratios and 95% confidence intervals were estimated for each SNP, and P values for trend (P-trend) were calculated. For statistically significant SNPs (P-trend < .05), the results were replicated with genotyped or imputed SNPs in the GWAS, and P values were adjusted for multiple testing. RESULTS: In the PLCO analysis, a significant association was observed between lung cancer and 81 SNPs located in 44 genes (P-trend < .05). Of these 81 SNPS, there was evidence for confirmation in the GWAS for 10 SNPs. However, after adjusting for multiple comparisons, the only SNP that retained a significant association with lung cancer in the replication phase was reference SNP rs4648127 (nuclear factor of kappa light polypeptide gene enhancer of B-cells 1 [NFKB1]) (multiple testing-adjusted P-trend = .02). The cytosine-thymine (CT)/TT genotype of NFKB1 was associated with reduced odds of lung cancer in the PLCO study (odds ratio, 0.56; 95% confidence interval, 0.37-0.86) and the in the GWAS (odds ratio, 0.79; 95% confidence interval, 0.69-0.90). CONCLUSIONS: A significant association was observed between a variant in the NFKB1 gene and the risk of lung cancer. The current findings add to evidence implicating inflammation and immunity in lung cancer etiology. Cancer 2012. Published 2012 by the American Cancer Society.