Abstract

ABSTRACT Introduction The formation of new blood vessels, a phenomenon known as angiogenesis, is essential for tumor growth and development of metastases. The most important regulator of this process 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. It was demonstrated that these genetic variants also have influence on susceptibility, development of metastases as well as survival in various types of cancer. Therefore, these variants could have an impact on relapse-free survival of patients with colorectal cancer (CRC). Methods To test this hypothesis, VEGF genotypes of the +936 C>T, -2578 C>A and -634 G>C polymorphisms were determined in genomic DNA extracted from peripheral blood of 433 Caucasian patients with histologically proven CRC. The different genotypes were analyzed by a fluorogenic exonuclease assay (TaqMan™). Results 159 patients (37%) developed metastases, relapsed or died during a follow-up of maximum 10 years (Mean follow-up time 58±34 months, median 55 months). In a cox regression model including the different VEGF genotypes, age at diagnosis, tumor grade, tumor size, stage (AJCC), number of lymph nodes evaluated, number of pathologic lymph nodes and administration of adjuvant 5-FU containing chemotherapy we were not able to detect a correlation between these polymorphisms and relapse-free survival. The relative risk (RR) for the +936 C>T SNP was 0.889 (95% CI: 0.619-1.279, p=0.527), for the -2578 C>A SNP 1.062 (95% CI: 0.780-1.446, p=0.704) and for the -634 G>C SNP 1.162 (95% CI: 0.846-1.595, p=0.355). Conclusion We conclude that the investigated polymorphisms show no association with relapse-free survival for Caucasians suffering from colorectal cancer.

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