Annals of Oncology Advance Access originally published online on April 6, 2006
Annals of Oncology 2006 17(9):1467-1468; doi:10.1093/annonc/mdl075
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© 2006 European Society for Medical Oncology
letters to the editor |
Vascular endothelial growth factor 936 C/T polymorphism in cancer patients
1 Department of General Surgery and Surgical Oncology, Numune State Hospital, Konya
2 Biotechnology Institute of Ankara University, Tandogan, Turkey
3 Department of Radiation Oncology, Ankara University Medical School, Cebeci, Turkey
4 Department of General Surgery, Ankara University Medical School, Turkey
5 Department of Pediatric Molecular Genetic, Ankara University Medical School, Cebeci, Ankara, Turkey
*(E-mail: aydaneroglu{at}hotmail.com or aydaneroglu{at}yahoo.com)
Angiogenesis is an essential process in the development, growth and metastasis of malignant tumors [1]. Vascular endothelial growth factor (VEGF) plays an important role in the angiogenesis. Increased VEGF expression is associated with tumor growth and metastasis, whereas inhibition of VEGF signaling results in suppression of both tumor-induced angiogenesis and tumor growth.
The human VEGF gene is located on chromosome 6p21.3 and is organized into 8 exons separated by 7 introns [2]. Several polymorphisms have been described in the VEGF gene. Three single-nucleotide polymorphisms (G+405C in the 5'-untranslated region, C–460T in the promoter region, and C+936T in the 3'-untranslated region) are common and related to VEGF protein production [3, 4].
Recent studies have shown that some VEGF polymorphism is related to the development of cancer. The 936 C/T polymorphism was correlated with a decreased breast cancer risk [5]. In two recent studies related to breast [6] and lung cancer [7], no significant differences in the allele, genotype or haplotype distribution of polymorphisms in VEGF gene between cases and control subjects were detected. To our knowledge no investigation of the role of VEGF 936 polymorphism in relation to malignant tumor has been undertaken in Turkish people. We have therefore conducted a study to evaluate the association between this polymorphism and cancer. We enrolled two groups. The first group (group I) was composed of 104 patients with various type cancer (breast cancer in 24 patients, lung cancer in 34, digestive system cancer in seven, urogenital tumor in five, sarcoma in seven, brain tumor in eight, lymphoma in four, nasopharyngeal tumor in five, and others in 10). The second group consisted of 125 healthy volunteers without history of malignancy (group 2).
Genomic DNA isolation was made from peripheral venous blood by standard phenol-chloroform extraction, and polymerase chain reaction of VEGF C936T polymorphism was performed according to previously described method [4] using forward primer 5'-AAG GAA GAG GAG ACT CTG CGC-3' and reverse primer 5'-TAT GTG GGT GGG TGT GTC TAC AGG-3'. Amplification was performed for 34 cycles with an annealing temperature of 60°C (Biometra, Germany). Amplified DNA was subjected to 2.5% agarose gel electrophoresis. Statistical analysis was performed using SPSS software (SPSS Inc., Chicago, IL). The groups were compared using chi-square test.
The frequency of VEGF 936C/T genotype in two groups was shown in Table 1. There was a statistically significant difference the VEGF 936C/T polymorphism between the groups (p < 0.0001). The carrier of VEGF 936 CT genotype was found to be an increased risk of development of malignant tumor. Our results are in contrast to previous published studies [5–7]. In addition, our findings, including the distribution of the genotype among control subjects, are different from the published studies. The frequency of 936 C/T polymorphism among healthy controls was 0.294 and 0.206 in the Austrian [5], and Korean [7] studies, respectively. Since genetic polymorphisms often vary among different ethnic groups, the different results in different populations may be due to different genetic background.
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In conclusion, we found that 936 C/T polymorphism is associated with the risk of malignant tumor and we suggest that VEGF gene may contribute to an inherited predisposition to malignant tumor, however additional studies with larger series from diverse ethnic populations are required to confirm our results.
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2. Vincenti V, Cassano C, Roschi M, Persico G. (1996) Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. Circulation 93:1493–1495.
3. Watson CJ, Webb NJA, Bottomley MJ, Brenchley PE. (2000) Identification of polymorphisms within the vascular endothelial growth factor (VEGF) gene: correlation with variation in VEGF protein production. Cytokine 12:1232–1235.[CrossRef][ISI][Medline]
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