title: VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese.
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.
authors.affiliation: Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.forename: Mayuko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Shingo
authors.initials: S
authors.lastname: Maeda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Noboru
authors.initials: N
authors.lastname: Okamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwaki
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Aoyama
authors.forename: Svetlana
authors.initials: S
authors.lastname: Markova
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Okumura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002087:Butyrates / Q000494:pharmacology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002087:Butyrates; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D000469:Alkaline Phosphatase