Carcinogenesis Advance Access originally published online on September 9, 2008
Carcinogenesis 2008 29(12):2330-2334; doi:10.1093/carcin/bgn210
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Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk
1 Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA
2 Departments of Medicine, Medical Biophysics and Epidemiology, Princess Margaret Hospital, University of Toronto, Toronto, ON M5G 2M9, Canada
3 Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
4 Division of Hematology and Oncology, MGH Cancer Center
5 Division of Gastroenterology, Endoscopy Unit, Department of Medicine
6 Thoracic Surgery Division, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
7 Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
8 Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
* To whom correspondence should be addressed. Tel: +1 617 432 1641; Fax: +1 617 432 6981; Email: rzhai{at}hsph.harvard.edu
Correspondence may also be addressed to David C.Christiani. Tel: +1 617 432 3323; Fax: +1 617 432 6981; Email: dchris{at}hsph.harvard.edu
Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis in esophageal adenocarcinoma (EA). Polymorphisms in the VEGF gene have been associated with altered VEGF expression and plasma VEGF levels. We hypothesized that polymorphisms of VEGF may contribute to EA risk. Functional polymorphisms in the VEGF gene (–460C/T, +405C/G and +936C/T) were determined in 308 patients with EA and 546 healthy controls. Logistic regression analysis was employed to assess the associations between genotypes, haplotypes of VEGF and EA risk, adjusting for multiple confounding factors. Compared with the +936CC genotype, the combined +936CT+TT genotypes were significantly associated with increased risk of developing EA, with adjusted odds ratio (OR) = 1.49 [95% confidence interval (CI), 1.05–2.12; P = 0.027]. The –460CT+CC were associated with increased risk of EA in smokers (adjusted OR = 1.57; 95% CI, 1.07–2.30; P = 0.021), whereas the –460CT/CC were associated with decreased risk of EA (adjusted OR = 0.47; 95% CI, 0.25–0.91; P = 0.025) in non-smokers. Compared with non-smokers with the +460TT, smokers with the +460CT+CC had significantly higher risk of EA (adjusted OR = 3.32; 95% CI, 1.56–7.10; P = 0.002). No overall or interacting association with EA risk was found for the +405C/G polymorphism. Haplotype CGT (–460C/+405G/+936T) was significantly associated with higher risk of EA (adjusted OR = 1.70; 95% CI, 1.04–2.73; P = 0.034). These results suggested that cigarette smoking modifies the association between VEGF polymorphisms and EA risk among Caucasians.
Abbreviations: CI, confidence interval; EA, esophageal adenocarcinoma; GERD, gastroesophageal reflux disease; OR, odds ratio; VEGF, vascular endothelial growth factor
Received June 19, 2008; revised August 5, 2008; accepted September 3, 2008.
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  P. A. Bradbury, R. Zhai, C. Ma, W. Xu, J. Hopkins, M. J. Kulke, K. Asomaning, Z. Wang, L. Su, R. S. Heist, et al. Vascular Endothelial Growth Factor Polymorphisms and Esophageal Cancer Prognosis Clin. Cancer Res., July 15, 2009; 15(14): 4680 - 4685. [Abstract] [Full Text] [PDF]
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