DNA methylation accelerated age as captured by epigenetic clocks influences breast cancer risk

Introduction: Breast cancer continues to be the leading form of cancer among women in the United States. Additionally, disparities across the breast cancer continuum continue to increase for women of historically marginalized populations. The mechanism driving these trends are unclear, however, accelerated biological age may provide key insights into better understanding these disease patterns. Accelerated age measured by DNA methylation using epigenetic clocks is to date the most robust method for estimating accelerated age. Here we synthesize the existing evidence on epigenetic clocks measurement of DNA methylation based accelerated age and breast cancer outcomes.

Methods: Our database searches were conducted from January 2022 to April 2022 and yielded a total of 2,908 articles for consideration. We implemented methods derived from guidance of the PROSPERO Scoping Review Protocol to assess articles in the PubMed database on epigenetic clocks and breast cancer risk.

Results: Five articles were deemed appropriate for inclusion in this review. Ten epigenetic clocks were used across the five articles demonstrating statistically significant results for breast cancer risk. DNA methylation accelerated age varied by sample type. The studies did not consider social factors or epidemiological risk factors. The studies lacked representation of ancestrally diverse populations.

Discussion: DNA methylation based accelerated age as captured by epigenetic clocks has a statistically significant associative relationship with breast cancer risk, however, important social factors that contribute to patterns of methylation were not comprehensively considered in the available literature. More research is needed on DNA methylation based accelerated age across the lifespan including during menopausal transition and in diverse populations. This review demonstrates that DNA methylation accelerated age may provide key insights for tackling increasing rates of U.S. breast cancer incidence and overall disease disparities experienced by women from minoritized backgrounds.