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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Article number15055
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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