title: Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women.
abstract: Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n = 61) and AAs (n = 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially-methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer.
authors.affiliation: a Comprehensive Cancer Center; The Ohio State University and James Cancer Hospital ; Columbus , Ohio , USA.
authors.forename: Min-Ae
authors.initials: MA
authors.lastname: Song
authors.affiliation: a Comprehensive Cancer Center; The Ohio State University and James Cancer Hospital ; Columbus , Ohio , USA.
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Brasky
authors.affiliation: a Comprehensive Cancer Center; The Ohio State University and James Cancer Hospital ; Columbus , Ohio , USA.|b Biochemistry and Pharmacology Department ; Victor Babes University of Medicine and Pharmacy ; 300041 Timisoara , Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.affiliation: a Comprehensive Cancer Center; The Ohio State University and James Cancer Hospital ; Columbus , Ohio , USA.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Weng
authors.affiliation: a Comprehensive Cancer Center; The Ohio State University and James Cancer Hospital ; Columbus , Ohio , USA.
authors.forename: Cenny
authors.initials: C
authors.lastname: Taslim
authors.affiliation: c Distilled Spirits Council of the United States ; Washington , DC , USA.
authors.forename: Ramona G
authors.initials: RG
authors.lastname: Dumitrescu
authors.affiliation: d Department of Epidemiology ; Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey ; New Brunswick , NJ 08903 , USA.
authors.forename: Adana A
authors.initials: AA
authors.lastname: Llanos
authors.affiliation: e Department of Epidemiology and Environmental Health; School of Public Health and Health Professions ; University at Buffalo ; Buffalo , NY 14214 , USA.
authors.forename: Jo L
authors.initials: JL
authors.lastname: Freudenheim
authors.affiliation: a Comprehensive Cancer Center; The Ohio State University and James Cancer Hospital ; Columbus , Ohio , USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Shields
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D059467:Transcriptome; D044465:White People / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor
keywords: breast; disparity; gene expression; genome-wide DNA methylation; race