Epigenetic aging in older breast cancer survivors and noncancer controls: Preliminary findings from the Thinking and Living with Cancer study Journal Article
| Authors: | Rentscher, K. E.; Bethea, T. N.; Zhai, W.; Small, B. J.; Zhou, X.; Ahles, T. A.; Ahn, J.; Breen, E. C.; Cohen, H. J.; Extermann, M.; Graham, D. M. A.; Jim, H. S. L.; McDonald, B. C.; Nakamura, Z. M.; Patel, S. K.; Root, J. C.; Saykin, A. J.; Van Dyk, K.; Mandelblatt, J. S.; Carroll, J. E. |
| Article Title: | Epigenetic aging in older breast cancer survivors and noncancer controls: Preliminary findings from the Thinking and Living with Cancer study |
| Abstract: | Background: Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes. Methods: Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency-matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy-Cognitive Function) and physical (Medical Outcomes Study Short Form-12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed-effects models tested survivor-control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve. Results: Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p =.001–.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p =.001–.04), and among this group, an older EEA related to worse self-reported cognition (p =.047) relative to controls. An older epigenetic age related to worse physical function in all women (p <.001–.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non-Hispanic White survivors. Conclusion: Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women. © 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society. |
| Keywords: | adult; cancer chemotherapy; controlled study; aged; cancer surgery; major clinical study; genetics; doxorubicin; fluorouracil; systemic therapy; cancer radiotherapy; methotrexate; breast cancer; mastectomy; aromatase inhibitor; psychology; cyclophosphamide; breast neoplasms; dna methylation; survivor; cancer survivor; self report; survivors; cancer hormone therapy; patient care; clinical study; infant; blood sampling; epigenetics; epigenesis, genetic; breast tumor; comorbidity; survivorship; tamoxifen; cognition; aging; genetic epigenesis; physical capacity; caucasian; geriatric assessment; lumpectomy; women's health; cancer survivors; geographic distribution; triple negative breast cancer; clinical outcome; cognitive function; ancestry group; older adults; physical function; estrogen receptor positive breast cancer; human epidermal growth factor receptor 2 positive breast cancer; very elderly; humans; human; female; article; black person; functional status assessment; human epidermal growth factor receptor 2 negative breast cancer; functional assessment of cancer therapy cognitive function; cognitive reserve; biological aging; epigenetic clock; developmental, age and growth parameters; dunedin pace of aging; epigenetic aging; extrinsic epigenetic age clock; medical outcomes study short form 12 |
| Journal Title: | Cancer |
| Volume: | 129 |
| Issue: | 17 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-09-01 |
| Start Page: | 2741 |
| End Page: | 2753 |
| Language: | English |
| DOI: | 10.1002/cncr.34818 |
| PUBMED: | 37259669 |
| PROVIDER: | scopus |
| PMCID: | PMC10659047 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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