PO.CL04.01 · 临床研究

乳腺癌幸存者中表观遗传衰老与端粒长度的纵向变化

Longitudinal change in epigenetic aging and telomere length in breast cancer survivors

编号 2462 展板 3 时间 4/20 09:00–12:00 区域 Section 41 主讲 Judith Carroll, PhD

分会场 Cancer and Aging: Implications for Outcomes

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作者与单位 Authors & Affiliations

Judith E. Carroll¹, Cynthia Kusters², Catherine M. Crespi³, Michael R. Irwin¹, Patricia A. Ganz⁴, Laura Petersen⁵, Julienne E. Bower⁶

¹Psychiatry & Biobehavioral Sciences, UCLA - University of California Los Angeles, Los Angeles, CA,²Epidemiology, UCLA - University of California Los Angeles, Los Angeles, CA,³University of California, Los Angeles, Los Angeles, CA,⁴Professor, Div. of Cancer Prevention & Control Res., UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA,⁵UCLA - University of California Los Angeles, Los Angeles, CA,⁶Psychology, UCLA - University of California Los Angeles, Los Angeles, CA

摘要 Abstract

中文摘要

目的：癌症治疗可能加速生物学衰老，但仍需要针对生物学衰老标志物的纵向研究，以更好地刻画生物学衰老随时间变化的模式。方法：我们随访了184名乳腺癌女性患者（0-III期），从确诊起至治疗后18个月。我们在三个治疗组中评估生物学衰老：化疗组（伴或不伴放疗）、放疗组（不伴化疗）以及既未化疗也未放疗组。获取了表观遗传年龄（PCPhenoAge、GrimAge、DunedinPACE）与端粒长度的测量值。采用线性混合模型估计组内从治疗前到治疗后即刻、治疗后6、12和18个月的变化。结果：接受化疗的女性在治疗后急性期表现出PCPhenoAge、GrimAge和DunedinPACE表观遗传年龄升高以及端粒长度缩短（P值<0.001）。这一变化虽有所减弱，但GrimAge、DunedinPACE和端粒长度在治疗后18个月时仍与基线存在显著差异。接受放疗的女性在治疗后6个月表现出PCPhenoAge升高的趋势以及显著的端粒长度缩短，且在18个月时仍保持改变（P值<0.05）。既未接受化疗也未接受放疗的女性中，表观遗传年龄或端粒长度均无显著变化。结论：我们观察到接受乳腺癌治疗的女性出现表观遗传年龄加速、衰老速度加快以及端粒缩短。该效应主要集中于接受化疗（伴或不伴放疗）的女性，提示这一治疗方案具有最大的损害效应。这些结果支持癌症治疗可能加速衰老的前提，并支持进一步开展研究以确定可用于缓解这些效应的关键临床和生物学靶点。

查看英文原文 English abstract

PURPOSE: Cancer treatments may accelerate biological aging, but longitudinal studies of biological markers of aging are needed to better characterize patterns of biological aging over time. METHODS: We followed 184 women with breast cancer (stage 0-III) from diagnosis to 18 months post treatment. We evaluated biological aging in three treatment groups: chemotherapy (with or without radiotherapy), radiotherapy (without chemotherapy), and neither chemotherapy or radiotherapy. Measures of epigenetic age (PCPhenoAge, GrimAge, DunedinPACE) and telomere length were obtained. Linear mixed models estimated within-group change from pre-treatment to immediate post, 6, 12, and 18 months post-treatment. RESULTS: Women who received chemotherapy exhibited increased epigenetic age in PCPhenoAge, GrimAge, and DunedinPACE and shortening of telomere length acutely following treatment (Ps<0.001). The change attenuated but remained significantly different than baseline for GrimAge, DunedinPACE, and telomere length out to 18 months. Women treated with radiotherapy exhibited a trend for increases in PCPhenoAge and significant telomere length shortening 6 months following treatment that remained modified at 18 months (Ps<0.05). There were no significant changes in epigenetic age or telomere length among women who did not receive either chemotherapy or radiation. CONCLUSION: We observed an acceleration of epigenetic age, an increase in the pace of aging, and telomere shortening among women receiving treatment for breast cancer. The effect was predominantly amongst women who received chemotherapy with or without radiation, pointing to this treatment regimen having the most damaging effects. These results support the premise that cancer treatment may accelerate aging and support further research to identify key clinical and biological targets to remediate these effects.

利益披露 Disclosure

J. E. Carroll, None.. C. Kusters, None.. M. R. Irwin, None.. L. Petersen, None.. J. Bower, None.

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