Association of the PDCD5 locus with lung cancer risk and prognosis in smokers.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Department of Experimental Oncology and Laboratories, Thoracic Surgery, Istituto Nazionale Tumori, Milan, Italy.
Monica
M
Spinola
Peter
P
Meyer
Stefan
S
Kammerer
F Stefania
FS
Falvella
Melanie B
MB
Boettger
Carolyn R
CR
Hoyal
Carmen
C
Pignatiello
Reiner
R
Fischer
Richard B
RB
Roth
Ugo
U
Pastorino
Karl
K
Haeussinger
Matthew R
MR
Nelson
Rainer
R
Dierkesmann
Tommaso A
TA
Dragani
Andreas
A
Braun
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D007558:Italy; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects
D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human