Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study

Kelly E Rentscher; Traci N Bethea; Wanting Zhai; Brent J Small; Xingtao Zhou; Tim A Ahles; Jaeil Ahn; Elizabeth C Breen; Harvey Jay Cohen; Martine Extermann; Deena M A Graham; Heather S L Jim; Brenna C McDonald; Zev M Nakamura; Sunita K Patel; James C Root; Andrew J Saykin; Kathleen Van Dyk; Jeanne S Mandelblatt; Judith E Carroll

doi:10.1002/cncr.34818

Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study

Cancer. 2023 Sep 1;129(17):2741-2753. doi: 10.1002/cncr.34818. Epub 2023 Jun 1.

Authors

Kelly E Rentscher^{1

2

3}, Traci N Bethea⁴, Wanting Zhai⁴, Brent J Small⁵, Xingtao Zhou⁴, Tim A Ahles⁶, Jaeil Ahn⁷, Elizabeth C Breen^{2

3}, Harvey Jay Cohen⁸, Martine Extermann⁹, Deena M A Graham¹⁰, Heather S L Jim⁹, Brenna C McDonald¹¹, Zev M Nakamura¹², Sunita K Patel¹³, James C Root⁶, Andrew J Saykin¹¹, Kathleen Van Dyk³, Jeanne S Mandelblatt⁴, Judith E Carroll^{2

3}

Affiliations

¹ Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
² Norman Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California, USA.
³ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California, USA.
⁴ Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
⁵ School of Aging Studies, University of South Florida, Tampa, Florida, USA.
⁶ Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
⁷ Department of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
⁸ Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, USA.
⁹ Moffitt Cancer Center, University of South Florida, Tampa, Florida, USA.
¹⁰ John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey, USA.
¹¹ Department of Radiology and Imaging Sciences, Indiana University School of Medicine and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, USA.
¹² Department of Psychiatry, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
¹³ City of Hope National Medical Center, Los Angeles, California, USA.

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.

Keywords: DNA methylation; biological aging; breast cancer; cognitive function; epigenetic clock; older adults; physical function.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aging / genetics
Breast Neoplasms* / drug therapy
Breast Neoplasms* / genetics
Breast Neoplasms* / psychology
Cancer Survivors* / psychology
DNA Methylation
Epigenesis, Genetic
Female
Humans
Infant
Survivors

Abstract

Publication types

MeSH terms

Grants and funding