Common single nucleotide polymorphisms in the vascular endothelial growth factor gene and colorectal cancer risk.
OBJECTIVE
Tumor growth requires the formation of new blood vessels, a phenomenon known as angiogenesis. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). Several common polymorphisms in the VEGF-gene have been associated with different VEGF expression, production and plasma levels according to allele status, and influence the risk of developing different types of cancer. Therefore, these variants might be risk factors for colorectal cancer (CRC).


METHODS
In the present case-control study, VEGF genotypes of the +936 C>T, -2578 C>A and -634 G>C polymorphisms were determined in 427 patients with histologically verified CRC and 427 age and sex-matched healthy control subjects. Genotypes were analyzed by a fluorogenic exonuclease assay (TaqMan). P-value for age at diagnosis was analyzed by student's t test, P-values for tumor characteristics were determined by Pearson's Chi-square test. Threshold for significance was P<0.05.


RESULTS
At the time of diagnoses, patients were between 29 and 83 years of age, with a mean age of 61+/-10.9 years. VEGF -2578 C>A and VEGF -634 G>C genotype frequencies were similar among patients and controls. Carriers of the 936T-allele were found slightly more frequent among controls (27.2%) than among patients (22.5%), but this difference did not reach statistical significance (P=0.07). Furthermore, no correlation was found between all these variants and tumor characteristics like size, histological grading, positive regional lymph node metastases or tumor stage.


CONCLUSIONS
We conclude that the investigated polymorphisms are not associated with individual susceptibility to colorectal cancer.
Hofmann
Guenter
G
Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. guenter.hofmann@meduni-graz.at
Langsenlehner
Uwe
U
Renner
Wilfried
W
Langsenlehner
Tanja
T
Yazdani-Biuki
Babak
B
Clar
Heimo
H
Gerger
Armin
A
Wehrschuetz
Martin
M
Samonigg
Hellmut
H
Krippl
Peter
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A