Abstract
Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has been implicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluate the relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India. We screened DNA samples of 192 sporadic breast cancer patients and 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>G polymorphisms using the PCR-RFLP method. For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003). For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observed with elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GG- CT of +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk of breast cancer (p=0.04; 0.0064). The findings of the present study indicated significant associations of VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab, North India.
Highlights
Angiogenesis, an essential process in tumor growth provides potential routes for tumor dissemination and metastasis (Folkman, 2002; Kerbel, 2008)
The aim of present study was to evaluate the relationship between Vascular endothelial growth factor (VEGF) +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India
For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%confidence interval (CI) 1.41-6.65; p=0.003)
Summary
Angiogenesis, an essential process in tumor growth provides potential routes for tumor dissemination and metastasis (Folkman, 2002; Kerbel, 2008). A common polymorphism +936C>T (rs3025039) located in 3́ UTR has been associated with different VEGF plasma levels (Renner et al, 2000; Krippl et al, 2003) This C to T substitution has been reported to alter binding of the transcription factor activating enhancer binding protein 4 (AP-4) which might affect mRNA structure (Renner et al, 2000). VEGF +936C>T polymorphism has been described as a potential predictive marker for clinical outcomes in gastric (Ruzzo et al, 2006; Tzanakis et al, 2006; Kim et al, 2007), breast (Lu et al, 2005) and ovarian cancer (Hefler et al, 2007) Another polymorphism +405C>G or -634C>G (rs2010963) located in potential binding site for MZF1 transcription factor in the 5́ UTR of VEGF has been significantly correlated with VEGF protein production (Watson et al, 2000). To the best of our knowledge, this is the first study on VEGF +405C>G and +936C>T polymorphisms in breast cancer from India
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