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Association of Genetic Polymorphisms in the VEGF Gene with Breast Cancer Survival

¹ Department of Medicine, Center for Health Services Research, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee and ² Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China

Requests for reprints: Xiao-Ou Shu, Vanderbilt University Center for Health Services Research, 6th Floor, Medical Center East, Nashville, TN 37232-8300. Phone: 615-936-0713; Fax: 615-936-1269; E-mail: xiao-ou.shu{at}vanderbilt.edu.

The vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis and vascular permeability. VEGF overexpression has been associated with advanced stage and poor survival of several cancers. We evaluated the association of functional polymorphisms in the VEGF gene with breast cancer survival in a cohort of 1,193 breast cancer patients who were recruited as part of a population-based case-control study in Shanghai, China from 1996 to 1998 and followed for cancer recurrence and mortality between March 2000 and December 2002. Included in the study were three functional polymorphisms (C–460T, G+405C, and C+936T) in the VEGF gene. Carrying the –460C or +405G allele was associated with decreased overall survival. The age-adjusted hazard ratios (HR) were 1.5 [95% confidence interval (95% CI), 0.9-2.5] for –460CC genotype carriers and 1.6 (95% CI, 1.0-2.5) for +405GG genotype carriers compared with noncarriers. Further analyses showed that the –460T/+450C/+936C haplotype was related to increased survival (HR, 0.57; 95% CI, 0.4-0.9), whereas the –460C/+405G/+936T haplotype was associated with nonsignificantly decreased survival (HR, 2.1; 95% CI, –0.9 to 4.7). The C+936T polymorphism alone was not related to overall or disease-free survival. This study suggests that VEGF polymorphisms may be a significant genetic marker for breast cancer prognosis.

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