{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:09:50Z","timestamp":1782947390816,"version":"3.54.5"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011541","name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute","doi-asserted-by":"publisher","award":["R03CA241956"],"award-info":[{"award-number":["R03CA241956"]}],"id":[{"id":"10.13039\/100011541","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007316","name":"Division of Cancer Prevention, National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA043703"],"award-info":[{"award-number":["P30CA043703"]}],"id":[{"id":"10.13039\/100007316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nBackground<\/jats:title>\nBreast cancer (BrCa) is the most common cancer for women globally. BrCa incidence varies by age and differs between racial groups, with Black women having an earlier age of onset and higher mortality compared to White women. The underlying biological mechanisms of this disparity remain uncertain. Here, we address this knowledge gap by examining the association between overall epigenetic age acceleration and BrCa initiation as well as the mediating role of race.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nWe measured whole-genome methylation (866,238 CpGs) using the Illumina EPIC array in blood DNA extracted from 209 women recruited from University Hospitals Cleveland Medical Center. Overall and intrinsic epigenetic age acceleration was calculated\u2013accounting for the estimated white blood cell distribution\u2013using the second-generation biological clock GrimAge. After quality control, 149 BrCa patients and 42 disease-free controls remained. The overall chronological mean age at BrCa diagnosis was 57.4 \u00b1 11.4 years and nearly one-third of BrCa cases were self-reported Black women (29.5%). When comparing BrCa cases to disease-free controls, GrimAge acceleration was 2.48 years greater (p<\/jats:italic>-value = 0.0056), while intrinsic epigenetic age acceleration was 1.72 years higher (p<\/jats:italic>-value = 0.026) for cases compared to controls. After adjusting for known BrCa risk factors, we observed BrCa risk increased by 14% [odds ratio (OR) = 1.14; 95% CI: 1.05, 1.25] for a one-year increase in GrimAge acceleration. The stratified analysis by self-reported race revealed differing ORs for GrimAge acceleration: White women (OR = 1.17; 95% CI: 1.03, 1.36), and Black women (OR = 1.08; 95% CI: 0.96, 1.23). However, our limited sample size failed to detect a statistically significant interaction for self-reported race (p-value<\/jats:italic> >0.05) when examining GrimAge acceleration with BrCa risk.<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nOur study demonstrated that epigenetic age acceleration is associated with BrCa risk, and the association suggests variation by self-reported race. Although our sample size is limited, these results highlight a potential biological mechanism for BrCa risk and identifies a novel research area of BrCa health disparities requiring further inquiry.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0308174","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T17:55:27Z","timestamp":1729792527000},"page":"e0308174","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Epigenetic aging differentially impacts breast cancer risk by self-reported race"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-6905","authenticated-orcid":true,"given":"Yanning","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan E.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah L.","family":"Gilmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3073-7463","authenticated-orcid":true,"given":"Fredrick R.","family":"Schumacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"pone.0308174.ref001","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","article-title":"Current and future burden of breast cancer: Global statistics for 2020 and 2040.","volume":"66","author":"M Arnold","year":"2022","journal-title":"Breast."},{"key":"pone.0308174.ref002","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-3-030-20301-6_3","article-title":"Health and Racial Disparity in Breast Cancer","volume":"1152","author":"CG Yedjou","year":"2019","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"pone.0308174.ref003","first-page":"7","article-title":"Cancer statistics, 2022.","volume":"72","author":"RL Siegel","year":"2022","journal-title":"CA: A Cancer Journal for Clinicians."},{"issue":"1","key":"pone.0308174.ref004","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.critrevonc.2007.09.001","article-title":"Impact of aging on the biology of breast cancer","volume":"66","author":"CC Benz","year":"2008","journal-title":"Crit Rev Oncol Hematol"},{"issue":"5","key":"pone.0308174.ref005","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1093\/jnci\/djn514","article-title":"Moderate alcohol intake and cancer incidence in women","volume":"101","author":"NE Allen","year":"2009","journal-title":"J Natl Cancer Inst"},{"issue":"4","key":"pone.0308174.ref006","first-page":"245","article-title":"American Cancer Society guideline for diet and physical activity for cancer prevention.","volume":"70","author":"CL Rock","year":"2020","journal-title":"CA: A Cancer Journal for Clinicians."},{"issue":"5","key":"pone.0308174.ref007","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/sj.bjc.6600124","article-title":"Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. 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