DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population-based study

Xinran Xu, Marilie D. Gammon, Hector Hernandez-Vargas, Zdenko Herceg, James G. Wetmur, Susan L. Teitelbaum, Patrick T. Bradshaw, Alfred I. Neugut, Regina M. Santella, Jia Chen

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Our purpose was to identify epigenetic markers of breast cancer risk, which can be reliably measured in peripheral blood and are amenable for large population screening. We used 2 independent assays, luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) to measure "global methylation content" in peripheral blood DNA from a well-characterized population-based case-control study. We examined associations between methylation levels and breast cancer risk among 1055 cases and 1101 controls and potential influences of 1-carbon metabolism on global methylation. Compared with women in the lowest quintile of LUMA methylation, those in the highest quintile had a 2.41-fold increased risk of breast cancer (95% confidence interval: 1.83-3.16; P, trend <0.0001). The association did not vary by other key tumor characteristics and lifestyle risk factors. Consistent with LUMA findings, genome-wide methylation profiling of a subset of samples revealed greater promoter hypermethylation in breast cancer case participants (P=0.04); higher LUMA was associated with higher promoter methylation in the controls (P=0.05). LUMA levels were also associated with functional sodium nitroprusside in key 1-carbon metabolizing genes, MTHFR C677T (P=0.001) and MTRR A66G (P=0.018). LINE-1 methylation was associated with neither breast cancer risk nor 1-carbon metabolism. Our results show that global promoter hypermethylation measured in peripheral blood was associated with breast cancer risk.

Original languageEnglish
Pages (from-to)2657-2666
Number of pages10
JournalFASEB Journal
Volume26
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • 1-carbon metabolism
  • Biomarker
  • Epigenetics

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