J Cancer 2015; 6(9):819-824. doi:10.7150/jca.12174

Research Paper

Promoter Hypermethylation in White Blood Cell DNA and Breast Cancer Risk

Yoon Hee Cho1,8, ✉, Lauren E. McCullough2, Marilie D. Gammon2, Hui-Chen Wu1, Yu-Jing Zhang1, Qiao Wang1, Xinran Xu3, Susan L. Teitelbaum3, Alfred I. Neugut4,5, Jia Chen3,6,7, Regina M. Santella1

1. Department of Environmental Health Sciences, Columbia University, 630 West 168th St, New York, NY 10032, USA
2. Department of Epidemiology, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill, NC 27599, USA
3. Department of Preventive Medicine, Mount Sinai School of Medicine, 1468 Madison Ave, New York, NY 10029, USA
4. Department of Epidemiology, Columbia University, 722 West 168th St, New York, NY 10032, USA
5. Department of Medicine, Columbia University, 161 Fort Washington Ave at W 165th St, New York, NY 10032, USA
6. Department of Pediatrics, Mount Sinai School of Medicine, One Gustave L. Levy Place
Box 1198, New York, NY 10029, USA
7. Department of Oncological Science, Mount Sinai School of Medicine, One Gustave L. Levy Place Box 1130, New York, NY 10029, USA
8. Current address: Departments of Biomedical and Pharmaceutical Sciences, University of Montana, 32 Campus Drive, Missoula, MT 59812, USA

Abstract

The role of gene-specific methylation in white blood cells (WBC) as a marker of breast cancer risk is currently unclear. We determined whether promoter hypermethylation in blood DNA of candidate tumor suppressor genes frequently methylated in breast tumors can be used as a surrogate biomarker for breast cancer risk. Promoter methylation of BRCA1, CDH1 and RARβ was analyzed in WBC DNA from a population-based sample of 1,021 breast cancer patients and 1,036 controls by the MethyLight assay. Gene-specific promoter methylation in the DNA of 569 tumor tissue samples was also analyzed to determine the correlation of methylation levels with blood from the same individual. Hypermethylation of BRCA1 (OR: 1.31; 95% CI: 0.98-1.75) in WBC was associated with an increased risk of breast cancer when positive methylation was defined as ≥0.1% methylated. There was lack of concordance between tumor tissue and paired WBC DNA methylation. These results provide limited support that hypermethylation of BRCA1 in WBC DNA may be useful for determination of breast cancer risk. Additional studies with larger numbers of genes are needed to fully understand the relationship between WBC methylation and breast cancer risk.

Keywords: Breast cancer, Promoter methylation, BRCA1, white blood cell DNA

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How to cite this article:
Cho YH, McCullough LE, Gammon MD, Wu HC, Zhang YJ, Wang Q, Xu X, Teitelbaum SL, Neugut AI, Chen J, Santella RM. Promoter Hypermethylation in White Blood Cell DNA and Breast Cancer Risk. J Cancer 2015; 6(9):819-824. doi:10.7150/jca.12174. Available from http://www.jcancer.org/v06p0819.htm