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儿童肿瘤幸存者衰老研究原图局部：化疗和放疗暴露示意
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CGM第414期：表观遗传时钟和儿童肿瘤幸存者的加速衰老

2024年5月29日CGM-US表观基因组
#表观基因组#肿瘤研究#人类遗传学
儿童肿瘤幸存者是否在加速衰老？报告用表观遗传时钟等衰老生物标志物讨论幸存者研究的发现。
Zhaoming Wang
Zhaoming Wang

圣裘德儿童研究医院流行病学与肿瘤控制系、计算生物学系

圣裘德儿童研究医院 Associate Member，主要任职于流行病学与肿瘤控制系，并兼任计算生物学系教职。他担任医院综合癌症中心肿瘤控制与幸存者研究项目遗传学和基因组学工作组共同主席，并是圣裘德终生队列研究及儿童肿瘤幸存者研究数据访问委员会成员。2005—2015 年，他在美国国家癌症研究所（NCI）肿瘤遗传学与流行病学部门担任生物信息学组负责人，从事肿瘤生殖系遗传学研究。2013 年，他为肿瘤学遗传关联与机制（GAME-ON）联盟设计 OncoArray，推动了 2017 年前后的一系列重要研究发表。他的研究集中于三个方向：原发与后续肿瘤的遗传流行病学；儿童肿瘤幸存者远期效应的生物标志物发现；治疗毒性的组学机制。2018 年，他牵头在 Journal of Clinical Oncology 发表了儿童肿瘤长期幸存者后续恶性肿瘤遗传易感性的研究，随后在 JAMA Oncology、Clinical Cancer Research 和 The Lancet Oncology 等期刊发表了评估后续及原发恶性肿瘤风险的生殖系遗传学研究。他进一步研究处于加速衰老状态、承受治疗及年龄相关慢性健康问题高负担的幸存者，并在 Clinical Cancer Research、Journal of the National Cancer Institute、Genome Medicine、JAMA Network Open 和 Nature Cancer 发表临床衰老研究。他是美国癌症研究协会衰老与肿瘤工作组成员，以及美国癌症学会肿瘤检测与进展评审委员会常任成员。按本次 2024 年报告的原始简介，他当时主持三项 NCI 资助的在研 R01 项目；自 2007 年起参与发表论文 220 余篇，获引用 38,000 余次，Google Scholar H 指数为 85。

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儿童肿瘤幸存者发生慢性健康问题（CHCs）和过早死亡的风险升高，其发生水平通常与年长数十岁的人群相当，提示存在加速衰老表型。我们测量了白细胞端粒长度、表观遗传年龄和克隆性造血等多种衰老生物标志物，以检验加速衰老现象，评估肿瘤治疗暴露与健康行为的影响，并进一步分析这些衰老标志物与特定慢性健康问题、全部慢性健康问题的严重程度和总体负担，以及过早死亡之间的关联。

CGM第414期：表观遗传时钟和儿童肿瘤幸存者的加速衰老 原文配图1

参考文献

  1. Song Nan, Li Zhenghong, Qin Na, Howell Carrie R., Wilson Carmen L., Easton John, Mulder Heather L., Edmonson Michael N., Rusch Michael C., Zhang Jinghui, Hudson Melissa M., Yasui Yutaka, Robison Leslie L., Ness Kirsten K., Wang Zhaoming. Shortened Leukocyte Telomere Length Associates with an Increased Prevalence of Chronic Health Conditions among Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort. Clinical Cancer Research. 2020;26(10):2362-2371. DOI: 10.1158/1078-0432.ccr-19-2503
  2. Qin Na, Li Zhenghong, Song Nan, Wilson Carmen L, Easton John, Mulder Heather, Plyler Emily, Neale Geoffrey, Walker Emily, Zhou Xin, Pan Haitao, Hudson Melissa M, Yasui Yutaka, Robison Leslie L, Zhang Jinghui, Ness Kirsten K, Wang Zhaoming. Epigenetic Age Acceleration and Chronic Health Conditions Among Adult Survivors of Childhood Cancer. JNCI: Journal of the National Cancer Institute. 2021;113(5):597-605. DOI: 10.1093/jnci/djaa147
  3. Dong Qian, Song Nan, Qin Na, Chen Cheng, Li Zhenghong, Sun Xiaojun, Easton John, Mulder Heather, Plyler Emily, Neale Geoffrey, Walker Emily, Li Qian, Ma Xiaotu, Chen Xiang, Huang I-Chan, Yasui Yutaka, Ness Kirsten K., Zhang Jinghui, Hudson Melissa M., Robison Leslie L., Wang Zhaoming. Genome-wide association studies identify novel genetic loci for epigenetic age acceleration among survivors of childhood cancer. Genome Medicine. 2022;14(1):32. DOI: 10.1186/s13073-022-01038-6
  4. Plonski Noel-Marie, Chen Cheng, Dong Qian, Qin Na, Song Nan, Parikh Hemang M., Shelton Kyla, Finch Emily R., Easton John, Mulder Heather, Zhang Jinghui, Neale Geoffrey, Walker Emily, Wang Hui, Krull Kevin, Ness Kirsten K., Hudson Melissa M., Robison Leslie L., Li Qian, Williams AnnaLynn, Wang Zhaoming. Epigenetic Age in Peripheral Blood Among Children, Adolescent, and Adult Survivors of Childhood Cancer. JAMA Network Open. 2023;6(4):e2310325. DOI: 10.1001/jamanetworkopen.2023.10325
  5. Williams AnnaLynn M., Mandelblatt Jeanne S., Wang Mingjuan, Dong Qian, Armstrong Gregory T., Bhakta Nickhill, Brinkman Tara M., Ehrhardt Matthew J., Mulrooney Daniel A., Gilmore Nikesha, Robison Leslie L., Yasui Yutaka, Small Brent J., Srivastava Deokumar, Hudson Melissa M., Ness Kirsten K., Krull Kevin R., Wang Zhaoming. Deficit Accumulation Index and Biological Markers of Aging in Survivors of Childhood Cancer. JAMA Network Open. 2023;6(11):e2344015. DOI: 10.1001/jamanetworkopen.2023.44015
  6. Plonski Noel-Marie, Pan Yue, Chen Cheng, Dong Qian, Zhang Xijun, Song Nan, Shelton Kyla, Easton John, Mulder Heather, Zhang Jinghui, Neale Geoffrey, Walker Emily, Wang Hui, Webster Rachel, Brinkman Tara, Krull Kevin R, Armstrong Gregory T, Ness Kirsten K, Hudson Melissa M, Li Qian, Huang I-Chan, Wang Zhaoming. Health-related quality of life and DNA methylation-based aging biomarkers among survivors of childhood cancer. JNCI: Journal of the National Cancer Institute. 2024;116(7):1116-1125. DOI: 10.1093/jnci/djae046
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