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  • Title: DNA methylation-based biological age, genome-wide average DNA methylation, and conventional breast cancer risk factors.
    Author: Chen M, Wong EM, Nguyen TL, Dite GS, Stone J, Dugué PA, Giles GG, Southey MC, Milne RL, Hopper JL, Li S.
    Journal: Sci Rep; 2019 Oct 21; 9(1):15055. PubMed ID: 31636290.
    Abstract:
    DNA methylation-based biological age (DNAm age), as well as genome-wide average DNA methylation, have been reported to predict breast cancer risk. We aimed to investigate the associations between these DNA methylation-based risk factors and 18 conventional breast cancer risk factors for disease-free women. A sample of 479 individuals from the Australian Mammographic Density Twins and Sisters was used for discovery, a sample of 3354 individuals from the Melbourne Collaborative Cohort Study was used for replication, and meta-analyses pooling results from the two studies were conducted. DNAm age based on three epigenetic clocks (Hannum, Horvath and Levine) and genome-wide average DNA methylation were calculated using the HumanMethylation 450 K BeadChip assay data. The DNAm age measures were positively associated with body mass index (BMI), smoking, alcohol drinking and age at menarche (all nominal P < 0.05). Genome-wide average DNA methylation was negatively associated with smoking and number of live births, and positively associated with age at first live birth (all nominal P < 0.05). The association of DNAm age with BMI was also evident in within-twin-pair analyses that control for familial factors. This study suggests that some lifestyle and hormonal risk factors are associated with these DNA methylation-based breast cancer risk factors, and the observed associations are unlikely to be due to familial confounding but are likely causal. DNA methylation-based risk factors could interplay with conventional risk factors in modifying breast cancer risk.
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