The Clinical and Pathological Profile of BRCA1 Gene Methylated Breast Cancer Women: A Meta-Analysis

Abstract

Background: DNA aberrant hypermethylation is the major cause of transcriptional silencing of the breast cancer gene 1 (BRCA1) gene in sporadic breast cancer patients. The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of BRCA1 gene hypermethylated breast cancer in women, and to pool the results to provide a unique clinical profile of this cancer population.

Methods: On September 2020, a systematic literature search was performed. Data were retrieved from PubMed, MEDLINE, and Scopus by searching the terms: "BRCA*" AND "methyl*" AND "breast". All studies evaluating the association between BRCA1 methylation status and breast cancer patients' clinicopathological features were considered for inclusion.

Results: 465 studies were retrieved. Thirty (6.4%) studies including 3985 patients met all selection criteria. The pooled analysis data revealed a significant correlation between BRCA1 gene hypermethylation and advanced breast cancer disease stage (OR = 0.75: 95% CI: 0.58-0.97; p = 0.03, fixed effects model), lymph nodes involvement (OR = 1.22: 95% CI: 1.01-1.48; p = 0.04, fixed effects model), and pre-menopausal status (OR = 1.34: 95% CI: 1.08-1.66; p = 0.008, fixed effects model). No association could be found between BRCA1 hypermethylation and tumor histology (OR = 0.78: 95% CI: 0.59-1.03; p = 0.08, fixed effects model), tumor grading (OR = 0.78: 95% CI :0.46-1.32; p = 0.36, fixed effects model), and breast cancer molecular classification (OR = 1.59: 95% CI: 0.68-3.72; p = 0.29, random effects model).

Conclusions: hypermethylation of the BRCA1 gene significantly correlates with advanced breast cancer disease, lymph nodes involvement, and pre-menopausal cancer onset.

Keywords: BRCA1; DNA; breast cancer; epigenetics; methylation; tumor progression.

Figure 1

PRISMA flow-chart of the study selection process.

Figure 2

Pooled results on forest plots about the correlation between breast cancer gene 1 (BRCA1) gene methylation status with breast cancer patients’ clinicopathological characteristics. Events= number of BRCA1 gene hypermethylated cases. Figure shows the correlation between BRCA1 gene methylation and histology (2a), disease stage (2b), tumor grading (2c), lymph nodal status (2d), molecular classification (2e) and menopausal status (2f).

Figure 2

Pooled results on forest plots about the correlation between breast cancer gene 1 (BRCA1) gene methylation status with breast cancer patients’ clinicopathological characteristics. Events= number of BRCA1 gene hypermethylated cases. Figure shows the correlation between BRCA1 gene methylation and histology (2a), disease stage (2b), tumor grading (2c), lymph nodal status (2d), molecular classification (2e) and menopausal status (2f).

Figure 3

Pooled results on forest plots about the correlation between BRCA1 gene methylation status with breast cancer patients’ clinicopathological characteristics. In this subanalysis, only studies adopting methylation-specific PCR (MS-PCR) methodology for the detection of BRCA1 methylation status were included. Events= number of BRCA1 gene hypermethylated cases. Figure shows the correlation between BRCA1 gene methylation and histology (3a), disease stage (3b), tumor grading (3c), lymph nodal status (3d), molecular classification (3e) and menopausal status (3f).

Figure 3

Pooled results on forest plots about the correlation between BRCA1 gene methylation status with breast cancer patients’ clinicopathological characteristics. In this subanalysis, only studies adopting methylation-specific PCR (MS-PCR) methodology for the detection of BRCA1 methylation status were included. Events= number of BRCA1 gene hypermethylated cases. Figure shows the correlation between BRCA1 gene methylation and histology (3a), disease stage (3b), tumor grading (3c), lymph nodal status (3d), molecular classification (3e) and menopausal status (3f).