Comprehensive analysis of DNA repair gene polymorphisms and survival in patients with early stage non-small-cell lung cancer.
This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNP) in DNA repair genes to determine the relationship between polymorphisms and the survival outcome of patients with early stage non-small-cell lung cancer (NSCLC). Three hundred and ten consecutive patients with surgically resected NSCLC were enrolled. Forty-eight SNP in 27 DNA repair genes were genotyped and their associations with overall survival (OS) and disease-free survival (DFS) were analyzed. Individually, six SNP exhibited significant associations with survival outcome. When the six SNP were combined, OS and DFS decreased as the number of bad genotypes increased (P(trend) <0.0001 for both). Patients with three, and four or five bad genotypes had a significantly worse OS and DFS compared with those carrying zero or one bad genotypes (adjusted hazard ratio [aHR] for OS=3.53, 95% confidence interval [CI]=1.25-9.97, P=0.02, and aHR for DFS=3.31, 95% CI=1.41-7.76, P=0.006; and aHR for OS=5.47, 95% CI=1.87-16.00, P=0.002, and aHR for DFS=4.42, 95% CI=1.82-10.74, P=0.001, respectively). These findings suggest that the six SNP identified can be used as prognostic markers for patients with surgically resected early stage NSCLC.
Kim
Min
M
Department of Internal Medicine, Kyungpook National University Hospital, Daegu, South Korea.
Kang
Hyo-Gyoung
HG
Lee
Shin Yup
SY
Lee
Hyung Cheol
HC
Lee
Eung Bae
EB
Choi
Yi Young
YY
Lee
Won Kee
WK
Cho
Sukki
S
Jin
Guang
G
Jheon
Hyo-Sung
HS
Son
Ji Woong
JW
Lee
Myung-Hoon
MH
Jung
Deuk Kju
DK
Cha
Seung Ick
SI
Kim
Chang Ho
CH
Kang
Young Mo
YM
Kam
Sin
S
Jung
Tae Hoon
TH
Jheon
Sanghoon
S
Park
Jae Yong
JY
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D015254:DNA Modification Methylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009367:Neoplasm Staging; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C086984:XPC protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes