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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

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

Published In FASEB J, (2012 Jun)

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.

PubMed ID: 22371529 Exiting the NIEHS site

MeSH Terms: Aged; Biomarkers, Tumor/blood; Breast Neoplasms/blood*; Breast Neoplasms/metabolism; Case-Control Studies; CpG Islands; DNA Methylation*; Female; Ferredoxin-NADP Reductase/genetics; Humans; Long Interspersed Nucleotide Elements; Methylenetetrahydrofolate Reductase (NADPH2)/genetics; Middle Aged; Risk

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