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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Research Article

Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study

Kathleen Conway, Sharon N. Edmiston, Chiu-Kit Tse, Christopher Bryant, Pei Fen Kuan, Brionna Y. Hair, Eloise A. Parrish, Ryan May and Theresa Swift-Scanlan
Kathleen Conway
1Department of Epidemiology, University of North Carolina at Chapel Hill
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  • For correspondence: kconway@med.unc.edu
Sharon N. Edmiston
2Lineberger Comprehensive Cancer Center, University of North Carolina
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Chiu-Kit Tse
1Department of Epidemiology, University of North Carolina at Chapel Hill
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Christopher Bryant
3Department of Biostatistics, University of North Carolina at Chapel Hill
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Pei Fen Kuan
4Applied Mathematics and Statistics, Stony Brook University
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Brionna Y. Hair
1Department of Epidemiology, University of North Carolina at Chapel Hill
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Eloise A. Parrish
5Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
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Ryan May
6The EMMES Corporation
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Theresa Swift-Scanlan
7School of Nursing, University of North Carolina at Chapel Hill
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DOI: 10.1158/1055-9965.EPI-14-1228
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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 1287 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. Results: Multivariable linear regression analysis of all tumors, controlling for age, menopausal status, stage, intrinsic subtype, and multiple comparisons (FDR), identified 7 CpG probes that showed significant (adjusted p<0.05) differential methylation between AAs and non-AAs. Stratified analyses detected an additional 4 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 (PBLs) 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. Impact: Epigenetic variation could contribute to differences in breast tumor development and outcomes between AAs and non-AAs.

  • Received October 31, 2014.
  • Revision received February 11, 2015.
  • Accepted March 3, 2015.
  • Copyright © 2015, American Association for Cancer Research.
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This OnlineFirst version was published on March 25, 2015
doi: 10.1158/1055-9965.EPI-14-1228

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Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study
Kathleen Conway, Sharon N. Edmiston, Chiu-Kit Tse, Christopher Bryant, Pei Fen Kuan, Brionna Y. Hair, Eloise A. Parrish, Ryan May and Theresa Swift-Scanlan
Cancer Epidemiol Biomarkers Prev March 25 2015 DOI: 10.1158/1055-9965.EPI-14-1228

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Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study
Kathleen Conway, Sharon N. Edmiston, Chiu-Kit Tse, Christopher Bryant, Pei Fen Kuan, Brionna Y. Hair, Eloise A. Parrish, Ryan May and Theresa Swift-Scanlan
Cancer Epidemiol Biomarkers Prev March 25 2015 DOI: 10.1158/1055-9965.EPI-14-1228
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