VEGF T-1498C polymorphism, a predictive marker of differentiation of colorectal adenocarcinomas in Japanese.
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.
Yamamori
Motohiro
M
Department of Hospital Pharmacy, School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Taniguchi
Mayuko
M
Maeda
Shingo
S
Nakamura
Tsutomu
T
Okamura
Noboru
N
Kuwahara
Akiko
A
Iwaki
Koichi
K
Tamura
Takao
T
Aoyama
Nobuo
N
Markova
Svetlana
S
Kasuga
Masato
M
Okumura
Katsuhiko
K
Sakaeda
Toshiyuki
T
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*
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