PURPOSE: Whole-genome scan association analysis was carried out to identify 
genetic variants predictive of lung cancer risk in smokers and to confirm the 
identified variants in an independent sample.
PATIENTS AND METHODS: A case-control study was performed using two pools 
consisting of DNA from 322 German smoking lung cancer patients and 273 healthy 
smoking controls, respectively. A replication study was carried out using 254 
Italian lung adenocarcinoma (ADCA) patients and 235 healthy controls.
RESULTS: Patients with genotypes GG or CG for the rs1862214 single nucleotide 
polymorphism, 5' upstream of the programmed cell death 5 (PDCD5) gene, compared 
with those with the common genotype CC showed an increased risk of lung cancer 
(odds ratio, 1.6; 95% CI, 1.2 to 2.1) and a higher incidence of poor clinical 
stage disease (hazard ratio [HR], 1.9; 95% CI, 1.1 to 3.4; P = .023), nodal 
involvement (HR, 1.9; 95% CI, 1.1 to 3.6; P = .033), and short-term survivorship 
(HR, 1.8; 95% CI, 1.2 to 2.6, P = .003). PDCD5 mRNA expression levels were 
approximately 2.4-fold lower in lung ADCA as compared to normal lung tissue. 
Human NCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased 
colony-forming ability.
CONCLUSION: These results suggest that the rs1862214 polymorphism in PDCD5 is 
predictive for lung cancer risk and prognosis, and that PDCD5 may represent a 
novel tumor suppressor gene influencing lung cancer.