VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese

Int J Med Sci. 2008 Apr 8;5(2):80-6. doi: 10.7150/ijms.5.80.

Abstract

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 TaqMan(R) 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; differentiation; genetic polymorphism; predictive marker; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adenocarcinoma / genetics*
  • Adult
  • Aged
  • Alkaline Phosphatase / metabolism
  • Asian Continental Ancestry Group / genetics
  • Butyrates / pharmacology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Colorectal Neoplasms / genetics*
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / metabolism
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Butyrates
  • RNA, Messenger
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • Alkaline Phosphatase