Article

Vascular endothelial growth factor 936 C/T polymorphism in cancer patients

Ankara University, Engüri, Ankara, Turkey
Annals of Oncology (Impact Factor: 7.04). 10/2006; 17(9):1467-8. DOI: 10.1093/annonc/mdl075
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    ABSTRACT: Angiogenesis is an essential process in the development, growth and metastasis of malignant tumors such as colon cancer. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. A case control study was carried out to determine whether there is an association between the VEGF 936C>T polymorphism and colon cancer. DNA samples taken from 262 colon cancer patients and 229 healthy controls were amplified by polymerase chain reaction for the VEGF 936C>T polymorphism. Genotype frequencies of the VEGF 936C>T polymorphism were significantly different between patient and control groups (CT+TT, odds ratio(OR): 1.524, 95% confidence interval (CI): 1.033-2.249). When stratified by gender and age, the frequencies of the T allele-bearing genotypes significantly increased risk for colon cancer in women and patients younger than 55 years (in women, OR: 1.996, 95% CI: 1.151-3.464 and in <55 years, OR: 4.156, 95% CI: 1.885-9.163). In addition, this association remained in most cases with distal and proximal colon cancer. Our study suggests that the VEGF 936C>T polymorphism might be a genetic determinant for colon cancer, at least in Koreans.
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    ABSTRACT: Identifying molecular markers for tumor recurrence is critical in successfully selecting patients with stage III colon cancer who are more likely to benefit from adjuvant chemotherapy. The present study analyzed a subset of 10 polymorphisms within eight genes involved in the tumor angiogenesis pathway and their impact on prognosis in stage III colon cancer patients treated with adjuvant chemotherapy. Blood samples were obtained from 125 patients with locally advanced colon cancer at University of Southern California medical facilities. DNA was extracted from peripheral blood and the genotypes were analyzed using PCR-restriction fragment length polymorphism and 5'-end [gamma-(33)P] ATP-labeled PCR protocols. Polymorphisms in vascular endothelial growth factor (VEGF) (C+936T; P = 0.003, log-rank test) and interleukin-8 (IL-8) (T-251A; P = 0.04, log-rank test) were independently associated with risk of recurrence in stage III colon cancer patients. In combined analysis, grouping alleles into favorable versus nonfavorable alleles, high expression variants of VEGF C+936T and IL-8 T-251A were associated with a higher likelihood of developing tumor recurrence (P < 0.001). High expression variants of VEGF C+936T and IL-8 T-251A were associated with shorter time to tumor recurrence, indicating that the analysis of angiogenesis-related gene polymorphisms may help to identify patient subgroups at high risk for tumor recurrence.
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