title: Genetic variation in innate immunity and inflammation pathways associated with lung cancer risk.
abstract: 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.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892, USA. shielsms@mail.nih.gov
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Shiels
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chaturvedi
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics; D012306:Risk; D012307:Risk Factors
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human