title: Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study.
abstract: BACKGROUND
  African American (AA) women are diagnosed with more advanced breast cancers and have worse survival than white women, but a comprehensive understanding of the basis for this disparity remains unclear. Analysis of DNA methylation, an epigenetic mechanism that can regulate gene expression, could help to explain racial differences in breast tumor clinical biology and outcomes.
  
  
  METHODS
  DNA methylation was evaluated at 1,287 CpGs in the promoters of cancer-related genes in 517 breast tumors of AA (n = 216) or non-AA (n = 301) cases in the Carolina Breast Cancer Study (CBCS).
  
  
  RESULTS
  Multivariable linear regression analysis of all tumors, controlling for age, menopausal status, stage, intrinsic subtype, and multiple comparisons [false discovery rate (FDR)], identified seven CpG probes that showed significant (adjusted P < 0.05) differential methylation between AAs and non-AAs. Stratified analyses detected an additional four CpG probes differing by race within hormone receptor-negative (HR(-)) tumors. Genes differentially methylated by race included DSC2, KCNK4, GSTM1, AXL, DNAJC15, HBII-52, TUSC3, and TES; the methylation state of several of these genes may be associated with worse survival in AAs. TCGA breast tumor data confirmed the differential methylation by race and negative correlations with expression for most of these genes. Several loci also showed racial differences in methylation in peripheral blood leukocytes (PBL) from CBCS cases, indicating that these variations were not necessarily tumor-specific.
  
  
  CONCLUSIONS
  Racial differences in the methylation of cancer-related genes are detectable in both tumors and PBLs from breast cancer cases.
  
  
  CONCLUSIONS
  Epigenetic variation could contribute to differences in breast tumor development and outcomes between AAs and non-AAs.
authors: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. kconway@med.unc.edu.
authors: Kathleen
authors: K
authors: Conway
authors: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors: Sharon N
authors: SN
authors: Edmiston
authors: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors: Chiu-Kit
authors: CK
authors: Tse
authors: Department of Biostatistics, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors: Christopher
authors: C
authors: Bryant
authors: Department of Applied Mathematics and Statistics, State University of New York, Stony Brook, New York.
authors: Pei Fen
authors: PF
authors: Kuan
authors: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors: Brionna Y
authors: BY
authors: Hair
authors: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors: Eloise A
authors: EA
authors: Parrish
authors: The EMMES Corporation, Rockville, Maryland.
authors: Ryan
authors: R
authors: May
authors: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors: Theresa
authors: T
authors: Swift-Scanlan
mesh_terms: D001741:Black or African American / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009657:North Carolina / Q000453:epidemiology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human