Evaluation of the epigenetic signatures of BRCA1 and TP53 as tools for metastatic prognosis: Translational study on a cohort of Moroccan women

Epigenetic inactivation of tumor suppressor genes plays a key role in cancer aggressiveness. This study evaluates the impact of methylation of BRCA1 and TP53 promoters on the risk of metastatic dissemination in women with breast cancer.
We analyzed the status of BRCA1 and TP53 gene promoter hypermethylation in patients with sporadic breast cancer. Associations were evaluated by the exact Fisher test and logistic regression (Odds Ratio). In addition, the co-occurrence was analyzed via the Spearman correlation coefficient.
The result reveals that 52% of samples are methylated and that these positives show that this epigenetic factor is remarkable in women over 47 years old. Overall, the Odd Ratio (OR) is 4.2, which means that the probability of presenting a methylation of BRCA1/TP53 genes is 4.2 times higher in patients with Metastasis than in those with Malignant Tumor stage. This demonstrates that a strong co-occurrence of methylation between BRCA1 and TP53 has been observed (ρ= 0.62). The analysis shows that BRCA1 methylation is significantly associated with the metastatic stage (p = 0.004) and associated with tumor aggressiveness.
The methylation of BRCA1, particularly when associated with that of TP53, constitutes a robust biomarker of tumor aggressiveness. These results suggest that the evaluation of the epigenetic profile could improve the prognostic stratification of patients.