Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Norman Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California, USA.
Cancer. 2023 Sep 1;129(17):2741-2753. doi: 10.1002/cncr.34818. Epub 2023 Jun 1.
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.
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.
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.
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.
癌症及其治疗可能会加速幸存者的衰老；然而，研究尚未检测到长期乳腺癌幸存者的衰老的表观遗传标志物。本研究检测了老年乳腺癌幸存者的表观遗传衰老是否比非癌症对照者更大，以及表观遗传衰老是否与功能结果相关。
在接受系统治疗之前招募的非转移性乳腺癌幸存者（n=89）和年龄在 62 至 84 岁之间的频率匹配对照者（n=101）提供了两份血样，以得出表观遗传衰老测量值（Horvath、外源性表观遗传年龄[EEA]、PhenoAge、GrimAge、Dunedin 衰老速度），并在大约 24 至 36 个月和 60 个月后完成认知（癌症治疗认知功能功能评估）和身体（医疗结果研究简短形式-12）功能评估。混合效应模型测试了幸存者与对照组在表观遗传衰老方面的差异，调整了年龄和合并症；功能结果模型还调整了种族群体、地点和认知储备。
在大约 24 至 36 个月时，幸存者在 Horvath、EEA、GrimAge 和 DunedinPACE 测量中比对照组的生物年龄大 1.04 至 2.22 岁（p=.001-.04）。接受化疗的幸存者的年龄大 1.97 至 2.71 岁（p=.001-.04），在这组中，与对照组相比，较老的 EEA 与较差的自我报告认知有关（p=.047）。所有女性的生理功能与较老的表观遗传年龄相关（p<.001-.01）。幸存者和对照组的表观遗传衰老随时间相似，但黑人幸存者的衰老速度比非西班牙裔白人幸存者快。
老年乳腺癌幸存者，特别是接受化疗的幸存者，表现出比对照组更大的表观遗传衰老，这可能与较差的结果有关。如果得到复制，生物衰老的测量可以补充老年评估，以指导老年女性的癌症护理。
