VEGF polymorphisms and survival in early-stage non-small-cell lung cancer.
OBJECTIVE
Polymorphisms in the VEGF gene have been identified that are believed to have functional activity. We hypothesized that such polymorphisms may affect survival outcomes among early-stage non-small-cell lung cancer (NSCLC) patients.


METHODS
We evaluated the relationship between VEGF polymorphisms and overall survival (OS) among patients with early-stage NSCLC treated with surgical resection at Massachusetts General Hospital from 1992 to 2001. We specifically investigated the VEGF polymorphisms +936C>T (rs3025039), -460T>C (rs833061), and +405G>C (rs2010963). Analyses of genotype associations with survival outcomes were performed using Cox proportional hazards models, Kaplan-Meier methods, and the log-rank test.


RESULTS
There were 462 patients and 237 deaths. Patients carrying the variant C allele of the VEGF +405G>C polymorphism had significantly improved survival (crude hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.90; P = .006; adjusted HR = 0.70; 95% CI, 0.54 to 0.91; P = .008). Five-year OS for patients carrying the variant C allele of the VEGF +405G>C polymorphism was 61% (95% CI, 54% to 67%) versus 51% (95% CI, 43% to 59%) for those who had the wild-type variant. There was a trend toward improved survival among patients carrying the variant T allele of the VEGF +936C>T polymorphism (crude HR = 0.74; 95% CI, 0.53 to 1.03; P = .07; adjusted HR = 0.73; 95% CI, 0.52 to 1.03; P = .07). Moreover, patients with higher number of variant alleles of the +405G>C and +936C>T polymorphisms had better survival. There was no association found with the -460T>C polymorphism.


CONCLUSIONS
Polymorphisms in VEGF may affect survival in early-stage lung cancer.
Heist
Rebecca Suk
RS
Massachusetts General Hospital, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA.
Zhai
Rihong
R
Liu
Geoffrey
G
Zhou
Wei
W
Lin
Xihong
X
Su
Li
L
Asomaning
Kofi
K
Lynch
Thomas J
TJ
Wain
John C
JC
Christiani
David C
DC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042461:Vascular Endothelial Growth Factor A