Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

Area of Science:

• Genomics
• Epigenetics
• Cancer Research

Background:

• Breast cancer incidence is higher in European Americans (EAs) than African Americans (AAs), but mortality is higher in AAs.
• Racial disparities in breast cancer are partly attributed to genetic and epigenetic factors, but differences in healthy breast tissue are understudied.

Purpose of the Study:

• To investigate genome-wide DNA methylation and gene expression differences in histologically normal breast tissues between healthy EAs and AAs.
• To explore potential links between these epigenetic variations and racial disparities in breast cancer.

Main Methods:

• Genome-wide DNA methylation and gene expression profiling were conducted on normal breast tissues from healthy EAs (n=61) and AAs (n=22).
• Linear regression models identified differentially methylated CpG sites (CpGs) between racial groups.
• Correlation analyses assessed methylation-gene expression relationships, and Ingenuity Pathway Analysis (IPA) determined biological functions.

Main Results:

• 485 differentially methylated CpGs were identified between EAs and AAs, with distinct patterns of hypermethylation in promoter regions for EAs and in gene bodies/intergenic regions for AAs.
• Differentially methylated CpGs were enriched in cancer-associated genes involved in cell death, survival, development, and signaling.
• Distinct methylation-expression correlation patterns and biological networks, linked by Ubiquitin C, were observed between EAs and AAs.

Conclusions:

• This study reveals significant, race-specific differences in DNA methylation and gene expression in healthy breast tissue.
• These epigenetic variations may represent a foundational element contributing to the observed racial disparities in breast cancer incidence and outcomes.