Promoter hypermethylation in white blood cell DNA and breast cancer risk

Yoon Hee Cho, Lauren E. McCullough, Marilie D. Gammon, Hui Chen Wu, Yu Jing Zhang, Qiao Wang, Xinran Xu, Susan L. Teitelbaum, Alfred I. Neugut, Jia Chen, Regina M. Santella

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)819-824
Number of pages6
JournalJournal of Cancer
Volume6
Issue number9
DOIs
StatePublished - 2015

Keywords

  • BRCA1
  • Breast cancer
  • Promoter methylation
  • White blood cell DNA

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