Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression to Breast Cancer in African American Women

Overview

Journal Cancer Genomics Proteomics

Specialties Biochemistry
Genetics
Oncology

Date 2025 Feb 24

PMID 39993808

Authors

Sylvia Dasi

Tammey J Naab

Bernard Kwabi-Addo

Victor Apprey

Desta Beyene

Robert L Dewitty Jr

Steven Nagel

Robin Williams

Kelly Bolden

Andrea Hayes-Dixon

Babak Shokrani

Delisha A Stewart

Olakunle O Kassim

Robert L Copeland

Yasmine M Kanaan

Affiliations

Soon will be listed here.

Abstract

Background/aim: Methylation in the estrogen receptor alpha (ESRα) promoter is an epigenetic abnormality associated with breast cancer (BCa), whereas hypermethylation results in the loss of ER expression.

Materials And Methods: Pyrosequencing was used to investigate a potential link between aberrant methylation in the P0/P1 promoters of ESRα and the risk of progression of benign fibrocystic and fibroadenoma tumors to BCa.

Results: Results showed a significantly elevated level of DNA methylation in ESRα P1 promoter (=0.0001) in fibroadenoma compared to ER-negative BCa tumors and a two-fold increased ESRα expression in fibrocystic and fibroadenoma benign tissues. In addition, methylation levels of HIN-1 and RASSF1A promoters were elevated in ER-positive compared to ER-negative BCa (-value<0.04). ANOVA Mixed Model revealed significantly higher methylation levels in the promoter of RASSF1A for fibroadenoma and ER-positive BCa (=0.004) compared to ER-negative BCa. Tumors with unclassified molecular subtypes (ER-positive, PR-negative, HER2-negative) had elevated levels of methylation (=0.046) in the P0 promoter compared with luminal B (ER-positive, PR-positive, HER2-positive) tumors. Grade 3 tumors showed a borderline association with ESRα P1 promoter methylation when compared with grade 2 tumors (=0.056).

Conclusion: ESRα P0 promoter hypermethylation may occur in the early stages of breast carcinogenesis, while P1 promoter methylation appears in later stages with a poor prognosis. Therefore, methylation of the ESRα promoter and other tumor-related genes could serve as a potential biomarker for predicting fibroadenoma progression risk to BCa.

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