The VEGFA rs3025039 Variant Is a Risk Factor for Breast Cancer in Mexican Women

Abstract

Breast cancer (BC) is the leading cause of death from tumors in women worldwide, influenced by various factors, including genetics. The T allele of the single nucleotide variant (SNV) rs3025039 at position +936 of the VEGFA gene has been reported to affect the mRNA regulatory mechanisms, potentially altering VEGFA expression and increasing BC risk. This study aimed to investigate the association between rs3025039 and BC in Mexican women residing in Jalisco, Mexico. The study included 231 women with a confirmed diagnosis of BC and 201 healthy subjects as a reference group (RG). PCR-RFLP was employed for the genotyping of rs3025039, with the visualization of amplified products using polyacrylamide gel electrophoresis. Significant differences were observed in rs3025039 alleles and genotypes between BC cases and the RG (p = 0.0038). The frequency of the T allele and the CT genotype was higher in the BC group compared to the RG, with a significant difference (p = 0.0006). In conclusion, this research suggests that the SNV rs3025039 is associated with a higher risk of BC in Mexican women. These findings enhance our understanding of the genetic underpinnings of BC in this population, offering potential insights for future studies and interventions.

Keywords: +936 C/T; Mexican woman; SNV; VEGFA; breast cancer; rs3025039.

Figure 1

VEGFA gene locus and the pathophysiological mechanism of tumor angiogenesis. (a) The rs3025039 variant, located in the 3′UTR region of VEGFA, where the C allele has been associated with an increase in mRNA, consequently leading to elevated plasma VEGFA levels; however, the T allele results in the loss of a potential binding site for the transcription factor AP-4, leading to a reduction in the plasma levels of VEGFA. (b) The process of angiogenesis from pre-existing blood vessels can be observed. Initially, there is vasodilation in response to the presence of nitric oxide, causing an increase in vascular permeability due to the presence of VEGFA, growth factors, interleukins, and MMPs (matrix metalloproteinases). The basement membrane is degraded by MMPs, allowing for intracellular contact between endothelial cells through a plasminogen activator, facilitating their migration and proliferation. Finally, peritoneal cells are recruited, resulting in the formation of a mature blood vessel and thus producing angiogenesis [17].

Figure 2

The electrophoresis results of the rs3025039 variant. In lane one, a molecular weight marker of 25 base pairs (bps) is depicted. Lanes 2–5, 7, 8, and 10–14 reveal a 208 bp band, representing the wild-type homozygous genotype C/C. Lines 6, 9, and 15 exhibit bands at 86, 122, and 208 bp, indicative of the heterozygous genotype C/T. Finally, line 16 shows the negative control.