Eugenio Espejo Speciality Hospital

Quito, Ecuador

Eugenio Espejo Speciality Hospital

Quito, Ecuador
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Lopez-Cortes A.,University of the Americas in Ecuador | Echeverria C.,University of the Americas in Ecuador | Ona-Cisneros F.,University of the Americas in Ecuador | Sanchez M.E.,University of the Americas in Ecuador | And 5 more authors.
Tumor Biology | Year: 2015

Breast cancer (BC) is the leading cause of cancer-related death among women in 2014. Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and MTR reductase (MTRR) are enzymes that play an important role in folate metabolism. The single nucleotide polymorphisms, MTHFR C677T, A1298C, MTR A2756G, and MTRR A66G, alter plasmatic folate and homocysteine concentrations, causing problems during the repairment, synthesis, and methylation of the genetic material. Therefore, it is essential to know how BC risk is associated with histopathological and immunohistochemical characteristics, genotype polymorphisms, and gene expression in a high altitude Ecuadorian mestizo population. DNA was extracted from 195 healthy and 114 affected women. Genotypes were determined by restriction enzymes and genomic sequencing. mRNA was extracted from 26 glandular breast tissue samples, both from cancerous tissue and healthy tissue adjacent to the tumor. Relative gene expression was determined with the comparative Livak method (2−ΔΔCT). We found significant association between the rs1801133 (A222V) genotypes and an increased risk of BC development: C/T (odds ratio [OR] = 1.8; 95 % confidence interval [CI] = 1.1–3.2; P = 0.039), T/T (OR = 2.9; 95 % CI = 1.2–7.2; P = 0.025), and C/T + T/T (OR = 1.9; 95 % CI = 1.1–3.3; P = 0.019). Regarding relative gene expression, we found significant mRNA subexpression between the combined genotypes C/T + T/T (rs1801133) and triple negative breast cancer (TNBC) (P = 0.034). In brief, the MTHFR gene and its protein could act as potential predictive biomarkers of BC, especially TNBC among the high altitude Ecuadorian mestizo population. © 2015, International Society of Oncology and BioMarkers (ISOBM).

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