Guan et al. BMC Cancer 2010, 10:431 http://www.biomedcentral.com/1471-2407/10/431 R E S E A R C H A R T I C L E Open Access Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy Xiaoxiang Guan1†, Ming Yin1†, Qingyi Wei1*, Hui Zhao1, Zhensheng Liu1, Li-E Wang1, Xianglin Yuan2, Michael S O’Reilly2, Ritsuko Komaki2, Zhongxing Liao2 Abstract Background: Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that VEGF polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients. Methods: We genotyped three potentially functional VEGF variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between VEGF variants and overall survival (OS). Results: Gender, Karnofsky’s performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, P = 0.022), compared with the VEGF -460 TT genotype. Conclusions: Our study suggests that VEGF -460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings. Background Non-small cell lung cancer (NSCLC) accounts for 89% of all lung cancer, and 30% of NSCLC patients present with locally-advanced unresectable tumors (unresectable stage IIIa and IIIb) [1]. Radiotherapy combined with chemotherapy, either sequentially or concurrently, is the standard treatment regimen for these patients, which, however, have resulted in unsatisfactory prognosis, with a 5-year survival rate of about 10-15% [1], and a median survival time (MST) of 16-18 months [2,3]. There has been a persistent interest in search for readily accessible molecular markers that may provide therapeutic benefits by predicting clinical outcomes of these locally advanced NSCLC (LA-NSCLC) on an individual basis. Angiogenesis is an essential process in the develop- ment, growth, and metastasis of malignant tumors * Correspondence: qwei@mdanderson.org † Contributed equally 1Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030, USA Full list of author information is available at the end of the article including lung cancer [4]. Vascular endothelial growth factor (VEGF) is one of the most potent and predomi- nant mediators of angiogenesis, which stimulate vascular endothelial cell growth, survival, and proliferation. Recent investigation has further revealed that VEGF acts as a mitogenic and survival signal for the tumor cell itself, indicating a broader range of tumor-promoting effects. Therefore, VEGF stands as a good candidate for prognostic biomarkers in cancer patients. Indeed, most tumors produce VEGF, whereas inhibition of the VEGF signaling significantly inhibits tumor growth in vivo [5]. In NSCLC, it has been found that a high expression of VEGF protein or mRNA was associated with increased tumor angiogenesis, early tumor relapse and reduced survival time [6-8]. A recent report further linked some functional VEGF polymorphisms with prognosis of early stage (stage I and II) NSCLC, probably through regula- tion of VEGF expression [9]. However, LA-NSCLC accounts for a significant proportion of lung cancer, and © 2010 Guan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.