Associations between environmental breast cancer risk factors and DNA methylation-based risk-predicting measures

Abstract

BackgroundGenome-wide average DNA methylation (GWAM) and epigenetic age acceleration have been suggested to predict breast cancer risk. We aimed to investigate the relationships between these putative risk-predicting measures and environmental breast cancer risk factors. MethodsUsing the Illumina HumanMethylation450K assay methylation data, we calculated GWAM and epigenetic age acceleration for 132 female twin pairs and their 215 sisters. Linear regression was used to estimate associations between these risk-predicting measures and multiple breast cancer risk factors.Within-pair analysis was performed for the 132 twin pairs. ResultsGWAM was negatively associated with number of live births, and positively with age at first live birth (both P<0.05). Epigenetic age acceleration was positively associated with body mass index (BMI), smoking, alcohol drinking and age at menarche, and negatively with age at first live birth (all P<0.05), and the associations with BMI, alcohol drinking and age at first live birth remained in the within-pair analysis. ConclusionsThis exploratory study shows that lifestyle and hormone-related breast cancer risk factors are associated with DNA methylation-based measures that could predict breast cancer risk. The associations of epigenetic age acceleration with BMI, alcohol drinking and age at first live birth are unlikely to be due to familial confounding.

Blood DNA methylation profiles improve breast cancer prediction

“…Methylation levels at combinations of many, sometimes hundreds, of CpGs have been shown to be useful in estimating biological age and a variety of other physiologic characteristics [19][20][21][22][23][24][25][26][27]. These DNAm estimators are reported to be associated with cancer risk factors [28][29][30] and health outcomes, including breast cancer [31][32][33], and we hypothesized they could be useful in the development of a methylation-based risk score for breast cancer.…”