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VEGF Polymorphisms and Survival in Early-Stage Non–Small-Cell Lung Cancer

Rebecca Suk Heist, Rihong Zhai, Geoffrey Liu, Wei Zhou, Xihong Lin, Li Su, Kofi Asomaning, Thomas J. Lynch, John C. Wain, David C. Christiani

From the Massachusetts General Hospital; Harvard School of Public Health, Boston, MA; Princess Margaret Hospital, Toronto, Ontario, Canada

Corresponding author: David C. Christiani, MD, MPH, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115; e-mail: dchris{at}hsph.harvard.edu

Purpose 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.

Patients and 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.

Conclusion Polymorphisms in VEGF may affect survival in early-stage lung cancer.

Supported by National Institutes of Health Grants No. CA074386 (D.C.C.), CA092824 (D.C.C.), CA090578 (D.C.C.), and K12CA087723 (R.S.H.), and the Flight Attendants Medical Research Institute Young Clinical Scientist Award (W.Z.).

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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