Int J Med Sci 2008; 5(2):80-86. doi:10.7150/ijms.5.80
VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese
1. Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
2. Division of Clinical Pharmacokinetics, Department of General Therapeutics, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
3. Department of Clinical Evaluation of Pharmacotherapy, Kobe University Graduate School of Medicine, 1-5-6 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
4. Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
5. Department of Endoscopy, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
6. Center for Integrative Education of Pharmacy Frontier (Frontier Education Center), Graduate School of Pharmaceutical Sciences, Kyoto University 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan
Background: Previously, MDR1 T-129C polymorphism, encoding multidrug resistant transporter MDR1/P-glycoprotein, was reported to be predictive of poorly-differentiated colorectal adenocarcinomas. Here, VEGF T-1498C, C-634G and C-7T polymorphisms, encoding vascular endothelial growth factor (VEGF), were investigated in terms of their association with differentiation grade.
Methods: VEGF genotypes were determined by TaqManR MGB probe based polymerase chain reaction and evaluated were confirmed by direct sequencing in 36 Japanese patients.
Results: VEGF T-1498C, but not C-634G or C-7T, was predictive of poorly-differentiated ones, and thereby a poor prognosis (p = 0.064 for genotype, p = 0.037 for allele), and this effect can be explained by that on VEGF expression. Treatment of a colorectal adenocarcinoma cell line, HCT-15, with sodium butyrate, a typical differentiating agent, resulted in an increase of alkaline phosphatase activity and MDR1 mRNA expression, but in a decrease of VEGF mRNA expression. The transfection of VEGF small interfering RNA (siRNA) induced the expression of MDR1 mRNA to 288-332% of the control level, whereas MDR1 siRNA had no effect on VEGF mRNA expression.
Conclusions: VEGF T-1498C polymorphism is also a candidate marker predictive of poorly-differentiated colorectal adenocarcinomas, but further investigations with a large number of patients should be addressed to draw a conclusion.
Keywords: colorectal adenocarcinoma, vascular endothelial growth factor, differentiation, genetic polymorphism, predictive marker
Yamamori M, Taniguchi M, Maeda S, Nakamura T, Okamura N, Kuwahara A, Iwaki K, Tamura T, Aoyama N, Markova S, Kasuga M, Okumura K, Sakaeda T. VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese. Int J Med Sci 2008; 5(2):80-86. doi:10.7150/ijms.5.80. Available from http://www.medsci.org/v05p0080.htm