Relationships between Global DNA Methylation in Circulating White Blood Cells and Breast Cancer Risk Factors.

Nayha Chopra-Tandon,Kathleen F Arcaro,Susan R Sturgeon,Haotian Wu

doi:10.1155/2017/2705860

Nayha Chopra-Tandon, Kathleen F Arcaro + Show 2 more

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https://doi.org/10.1155/2017/2705860

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Abstract

It is not yet clear whether white blood cell DNA global methylation is associated with breast cancer risk. In this review we examine the relationships between multiple breast cancer risk factors and three markers of global DNA methylation: LINE-1, 5-mdC, and Alu. A literature search was conducted using Pubmed up to April 1, 2016, using combinations of relevant outcomes such as “WBC methylation,” “blood methylation,” “blood LINE-1 methylation,” and a comprehensive list of known and suspected breast cancer risk factors. Overall, the vast majority of reports in the literature have focused on LINE-1. There was reasonably consistent evidence across the studies examined that males have higher levels of LINE-1 methylation in WBC DNA than females. None of the other demographic, lifestyle, dietary, or health condition risk factors were consistently associated with LINE-1 DNA methylation across studies. With the possible exception of sex, there was also little evidence that the wide range of breast cancer risk factors we examined were associated with either of the other two global DNA methylation markers: 5-mdC and Alu. One possible implication of the observed lack of association between global WBC DNA methylation and known breast cancer risk factors is that the association between global WBC DNA methylation and breast cancer, if it exists, is due to a disease effect.

Highlights

A CpG site, a cytosine followed by a guanine, has the potential to be methylated, and measuring 5-methyl-2󸀠 deoxycytidine (5-mdC) content across the genome by liquid chromatography/mass spectrometry (LC/MS) can provide an overall measure of genome-wide DNA methylation levels
In the NIEHS sister case-cohort study of 294 cases and 646 noncases in which the mean time between blood collection and breast cancer diagnosis was 15 months [8], LINE-1 methylation percentage in white blood cell (WBC) DNA was inversely associated with the risk of breast cancer, with a nearly twofold increased risk observed among women in the lowest quartile compared with those in the highest quartile
We examined the relationships between these breast cancer risk factors and three markers of global DNA methylation: LINE-1, 5-mdC, and Alu

Summary

Introduction

A CpG site, a cytosine followed by a guanine, has the potential to be methylated, and measuring 5-methyl-2󸀠 deoxycytidine (5-mdC) content across the genome by liquid chromatography/mass spectrometry (LC/MS) can provide an overall measure of genome-wide DNA methylation levels. Measuring DNA methylation levels in LINE-1 or Alu repetitive elements by pyrosequencing or Methyl Light is often used as a surrogate higher-throughput approach to assess genome-wide methylation [2]. In a casecontrol study of breast cancer of cases and controls, Choi and colleagues observed a nearly threefold increase in risk among women in the lowest tertile of total 5-mdC levels in WBC DNA compared to women in the highest tertile [1]. In the NIEHS sister case-cohort study of 294 cases and 646 noncases in which the mean time between blood collection and breast cancer diagnosis was 15 months [8], LINE-1 methylation percentage in WBC DNA was inversely associated with the risk of breast cancer, with a nearly twofold increased risk observed among women in the lowest quartile compared with those in the highest quartile. Several other case-control studies, ranging in the number of breast cancer cases from 19 to 1064, found no association between

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