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  • American Association for Cancer Research (AACR)  (2)
  • Zhai, Wanting  (2)
  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 2_Supplement_1 ( 2023-01-15), p. B018-B018
    Abstract: Cancer and its treatments are thought to increase risk for accelerated aging in survivors, and biological aging may be a key mechanism; however, no research to date has examined epigenetic markers of aging in long-term breast cancer survivors. We used data from the Thinking and Living with Cancer (TLC) study to examine whether older breast cancer survivors have accelerated epigenetic aging compared to non-cancer controls several years after treatment completion and whether epigenetic aging related to cognitive and physical function. Non-metastatic breast cancer survivors ages 62–84 years (n=89) and frequency-matched controls (n=101) provided two blood samples between 24- and 60-months post-diagnosis. DNA methylation profiling (Illumina Infinium EPIC array) derived epigenetic aging measures: Horvath, Hannum, PhenoAge, GrimAge, and Dunedin Pace of Aging Methylation. Participants completed neuropsychological testing and questionnaires to assess cognitive and physical function at each visit. Mixed-effects models adjusted for chronological age and comorbidities and applied false discovery rate correction for multiple testing. Survivors were 1.04–2.22 years older biologically than controls at the first blood sample based on Horvath, Hannum, and GrimAge measures (corrected ps=.025, .025, and .058, respectively), with marginal differences for Dunedin Pace of Aging (corrected p=.096); however, survivors and controls showed similar changes in epigenetic aging over time. Exposure to prior chemotherapy (with or without hormonal therapy; n=29) was associated with an epigenetic age 1.97–2.71 years older than controls (corrected ps=.005 to .065). Among survivors who received chemotherapy, an older Hannum epigenetic age was associated with poorer self-reported cognition relative to controls (coeff=-0.64, uncorrected p=.047; n.s. after correction). Older breast cancer survivors, particularly those receiving chemotherapy, showed an accelerated epigenetic aging profile compared to their peers without cancer at 24 months or more post-diagnosis, following the completion of active therapy. This study also provides preliminary evidence that survivors who received chemotherapy may be at increased risk for poorer age-related survivorship outcomes. Citation Format: Kelly E. Rentscher, Wanting Zhai, Brent J. Small, Jaeil Ahn, Tim A. Ahles, Traci N. Bethea, Elizabeth C. Breen, Harvey J. Cohen, Martine Extermann, Deena M.A. Graham, Paul B. Jacobsen, Heather S.L. Jim, Brenna C. McDonald, Zev M. Nakamura, Sunita K. Patel, James C. Root, Andrew J. Saykin, Danielle B. Tometich, Kathleen M. Van Dyk, Xingtao Zhou, Jeanne S. Mandelblatt, Judith E. Carroll. Long-term epigenetic aging in older breast cancer survivors and non-cancer controls: Preliminary findings from the Thinking and Living with Cancer (TLC) Stud [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 B018.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 2
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 32, No. 1_Supplement ( 2023-01-01), p. B111-B111
    Abstract: Introduction: While some cancer survivors experience minimal lasting effects of diagnosis and treatment, others report persistent decrements in physical and cognitive function. These changes may represent aging beyond that expected for the chronological age (i.e., “accelerated aging”). Racial minority groups often have an accelerated aging phenotype even before cancer diagnosis, partly due to chronic stress and other multi-level factors that affect aging and the ability to repair physiologic damage, leaving them more vulnerable to poor survivorship outcomes. However, we know little about physical and cognitive aging in this group and few studies have collected objective measures of physical and cognitive aging in minority cancer survivors. Methods: We examined changes in physical and cognitive function across 60 months of follow-up among Black and White survivors in the Thinking and Living with Cancer Study (TLC). TLC is an ongoing prospective multi-site cohort study recruiting non-metastatic breast cancer survivors aged ≥60 years. Participants completed questionnaires and objective assessments prior to systemic therapy with annual follow-up for up to 60 months. Physical function was measured using the timed up and go test (TUG); cognitive function was measured with Z scores on 11 neuropsychological tests for two domains: learning and memory (LM) and attention, processing, and executive function (APE). Mixed linear regression models predicting TUG, APE, or LM adjusted for age, study site, time, and cognitive reserve using the Wide Range Achievement Test (WRAT). Results: Black and White survivors in TLC were similar in age, education, comorbidities, and year of enrollment (p & gt;0.14), but differed by study site (p & lt;0.01) and WRAT score (p & lt;0.01). On average, Black survivors had slower performance than White survivors on the TUG test (34 Black survivors, 366 White survivors; 12.6 seconds (SD=0.41) vs. 11.0 seconds (SD=0.13), respectively; p & lt;0.001) at 12 months, but racial differences declined over time. Black survivors had poorer performance than White survivors for both LM and APE across 60 months of follow-up (94 Black survivors, 995 White survivors; p & lt;0.001): mean Z scores were -0.23 (SD=0.08) among Black survivors and 0.31 (SD=0.03) among White survivors for LM and -0.29 (SD=0.06) among Black survivors and 0.1 (SD=0.02) among White survivors for APE. In multivariable models, race was a significant predictor of TUG score (β=0.94, p & lt;0.01), LM score (β=-0.58, p & lt;0.01), and APE score (β=-0.38, p & lt;0.01). Conclusions: Older Black breast cancer survivors tended to have worse physical and cognitive function compared to older White breast cancer survivors and may experience accelerated decline. Additional studies are needed to address critical evidence gaps about the prevalence of poor physical and cognitive function, as well as aging trajectories, among Black breast cancer survivors. Citation Format: Traci N. Bethea, Wanting Zhai, Xingtao Zhou, Tim A. Ahles, Jaeil Ahn, Harvey J. Cohen, Asma A. Dilawari, Deena Graham, Heather Jim, Brenna C. McDonald, Zev M. Nakamura, Sunita K. Patel, Kelly E. Rentscher, James C. Root, Andrew J. Saykin, Brent J. Small, Kathleen Van Dyk, Jeanne S. Mandelblatt, Judith E. Carroll. Black-White differences in physical and cognitive aging among older breast cancer survivors in the Thinking and Living with Cancer Study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B111.
    Type of Medium: Online Resource
    ISSN: 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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