Methylation of the BMP6, BRCA1, ESR2, GSTP1 and TIMP3 genes in Mexican women with breast cancer and benign disease.

Breast cancer (BC) is the main cause of cancer-related mortality in women and is influenced by genetic, environmental and lifestyle factors. The inactivation of tumor suppressor genes, such as bone morphogenetic protein 6 (BMP6), breast cancer susceptibility gene 1 (BRCA1), estrogen receptor 2 (ESR2), glutathione S-transferase π1 (GSTP1) and tissue inhibitor of metalloproteinase 3 (TIMP3), via methylation may contribute to the development of BC. The present study analyzed the methylation status of these genes in 60 BC and benign disease (BD) tissue samples from Mexican women and the association with clinical and histopathological variables. DNA was modified with sodium bisulfite, followed by methylation-specific PCR and electrophoresis, and analyzed using χ2 test, Fisher's exact test, logistic regression, odds ratio (OR) with 95% confidence interval and Kaplan-Meier curves. The results indicated that the average age was higher in the BC group compared with that in the BD group (55 vs. 42 years; P<0.00001), with ≥50 years being a significant risk factor (OR, 5.44; P=0.00002). Only BRCA1 demonstrated a significant difference in methylation status, increasing the susceptibility to BC (OR, 2.50; P=0.0001), and tending to be associated with increased proliferation and lymph node metastasis. TIMP3 methylation was significantly associated with distant metastasis (OR, 8.65; P=0.028). Methylation of BRCA1 and TIMP3 demonstrated a significant association with poor prognosis in BC. BRCA1 was methylated more frequently in women with BC and TIMP3 was associated with a higher risk of distant metastasis. The present study highlighted the potential of these genes as prognostic biomarkers and the need to further explore DNA methylation for diagnostic and therapeutic purposes in future research.