Polymorphisms in apoptosis-related genes and survival of patients with early-stage non-small-cell lung cancer.
OBJECTIVE
This study was conducted to determine the association between single-nucleotide polymorphisms (SNPs) in apoptosis-related genes and survival outcomes of patients with early-stage non-small-cell lung cancer (NSCLC).


METHODS
Three hundred ten consecutive patients with surgically resected NSCLC were enrolled. Twenty-five SNPs in 17 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed.


RESULTS
Three SNPs (TNFRSF10B rs1047266, TNFRSF1A rs4149570, and PPP1R13L rs1005165) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased as the number of bad genotypes increased (P (trend) for OS and DFS = 7 × 10(-5) and 1 × 10(-4), respectively). Patients with one bad genotype, and patients with two or three bad genotypes had significantly worse OS and DFS compared with those with no bad genotypes [adjusted hazard ratio (aHR) for OS = 2.27, 95% confidence interval (CI) = 1.22-4.21, P = 0.01, aHR for DFS = 1.74, 95% CI = 1.08-2.81, P = 0.02; aHR for OS = 4.11, 95% CI = 2.03-8.29, P = 8 × 10(-5); and aHR for DFS = 2.89, 95% CI = 1.64-5.11, P = 3 × 10(-4), respectively].


CONCLUSIONS
Three SNPs in apoptosis-related genes were identified as possible prognostic markers of survival in patients with early-stage NSCLC. The SNPs, and particularly their combined genotypes, can be used to identify patients at high risk for poor disease outcome.
Lee
Eung Bae
EB
Department of Thoracic Surgery, Kyungpook National University Hospital, Daegu, Korea.
Jeon
Hyo-Sung
HS
Yoo
Seung Soo
SS
Choi
Yi Young
YY
Kang
Hyo-Gyoung
HG
Cho
Sukki
S
Cha
Sung-Ick
SI
Choi
Jin Eun
JE
Park
Tae-In
TI
Lee
Byung-Heon
BH
Park
Rang-Woon
RW
Kim
In-San
IS
Kang
Young Mo
YM
Kim
Chang Ho
CH
Jheon
Sanghoon
S
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D015996:Survival Rate
D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D047888:Receptors, Tumor Necrosis Factor, Type I; D012097:Repressor Proteins; C505639:TNFRSF10B protein, human; C506235:TNFRSF1A protein, human