Abstract
Abstract Introduction: Age is a strong predictor for breast cancer (BCa) risk. The median age at diagnosis varies by race/ethnicity. In the United States (U.S.), non-White women are more likely to be diagnosed at a younger age than non-Hispanic White (NHW) women. Epigenetic age, measured as changes to DNA via methylation (DNAm) using epigentic clocks, is highly accurate at estimating cellular age using several tissues and cell types may differ from chronological age. Epigenetic age is more robust than other molecular markers of aging, such as telomere length. Differences between epigenetic age and chronological age, termed epigenetic age acceleration, may be the driver of age and race/ethnicity discrepancies when estimating BCa risk. Age-related methylation between disease-free and tumor breast tissue is significantly differentially methylated. For example, aberrant methylation of promoter regions of polycomb group protein target genes and CpG islands associated with BCa risk and progression. Therefore, the purpose of this scoping review is to gather data on epigenetic clocks as a predictor for BCa incidence. Study objective: Synthesize the existing evidence on epigenetic accelerated aging measured with epigenetic clocks and breast cancer risk in the U.S. Methods: The PROSPERO Scoping Review Protocol was used for this project. We performed multiple PubMed searches utilizing search language developed by an experienced search librarian. The searches were conducted from January 2022 to April 2022. The searches yielded a total of 2,908 studies in the search process. The eligibility for inclusion applied during article review was: 1) the study must have used an epigenetic clock to assess epigenetic accelerated age in their sample, 2) the study’s primary outcome needed to be breast cancer risk, 3) the study needed to use a U.S. based study sample 3) the study needed to be published in a peer-reviewed PubMed indexed journal, 4) the study must have been published by April 30, 2022. Results: A total of seven articles from the 2,908 were determined eligible for inclusion. Data extraction from these seven articles demonstrated epigenetic accelerated age measured with epigenetic clocks does have an associative relationship with the development of breast cancer. Discussion: BCa risk is also known to drastically increase after menopause, although there are significant differences of menopausal transition in race/ethnicity. On average, African American, Asian, and Latina women begin menopause earlier than non-Hispanic White women. Emerging evidence suggests that earlier menopause in these populations may be a result of structural factors experienced by historically disadvantaged communities. The studies included in this review focused primarily on NHW women. More research is needed to better understand the role of DNAm and accelerated epigenetic age in diverse populations. Citation Format: Jennifer Daw, Devin Saunders, Adria Vasquez, Celina Valencia. Epigenetic clocks and breast cancer outcomes: A scoping review. [R] [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B013.
Published Version
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