DNA methylation-based biological age, genome-wide average DNA methylation, and conventional breast cancer risk factors

Minyuan Chen, Ee Ming Wong, Tuong L. Nguyen, Gillian S. Dite, Jennifer Stone, Pierre-Antoine Dugué, Graham G. Giles, Melissa C. Southey, Roger L. Milne, John L. Hopper, Shuai Li

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15 Citations (Scopus)


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.

Original languageEnglish
Article number15055
Number of pages10
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2019

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