表观遗传年龄与中风后的长期癌症风险。

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Antoni Suárez-Pérez, Adrià Macias-Gómez, Isabel Fernández-Pérez, Marta Vallverdú-Prats, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Maia Campanale, Daniel Guisado-Alonso, Ana Rodríguez-Campello, Joan Jiménez-Balado, Jordi Jiménez-Conde, Angel Ois
{"title":"表观遗传年龄与中风后的长期癌症风险。","authors":"Antoni Suárez-Pérez, Adrià Macias-Gómez, Isabel Fernández-Pérez, Marta Vallverdú-Prats, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Maia Campanale, Daniel Guisado-Alonso, Ana Rodríguez-Campello, Joan Jiménez-Balado, Jordi Jiménez-Conde, Angel Ois","doi":"10.1186/s13073-024-01408-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The association between increased cancer risk following a cerebrovascular event (CVE) has been previously reported. We hypothesize that biological age (B-age) acceleration is involved in this association. Our study aims to examine B-age as a novel contributing factor to cancer development post-CVE.</p><p><strong>Methods: </strong>From our prospective stroke registry (BasicMar), we selected 940 cases with epigenetic data. For this study, we specifically analyzed 648 of these patients who had available data, no prior history of cancer, and a minimum follow-up of 3 months. The primary outcome was cancer incidence. B-age was estimated using DNA methylation data derived from whole blood samples obtained within 24 h of stroke onset, employing various epigenetic clocks (including Hannum, Horvath, PhenoAge, Zhang<sub>BLUP</sub>, Zhang<sub>EN</sub>, and the mitotic epiTOC). Extrinsic epigenetic age acceleration (EEAA) was calculated as the residuals from the regression of B-age against chronological age (C-age). For epiTOC, the age-adjusted values were obtained by regressing out the effect of age from the raw epiTOC measurements. Estimated white cell counts were derived from DNA methylation data, and these cell fractions were used to compute the intrinsic epigenetic age acceleration (IEAA). Subsequently, we evaluated the independent association between EEAA, IEAA, and cancer incidence while controlling for potential confounding variables.</p><p><strong>Results: </strong>Among 648 patients with a median follow-up of 8.15 years, 83 (12.8%) developed cancer. Cox multivariable analyses indicated significant associations between Hannum, Zhang, and epiTOC EEAA and the risk of cancer after CVE. After adjusting for multiple testing and competing risks, EEAA measured by Hannum clock maintained an independent association with cancer risk. Specifically, for each year increase in Hannum's EEAA, we observed a 6.0% increased incidence of cancer (HR 1.06 [1.02-1.10], p value = 0.002).</p><p><strong>Conclusions: </strong>Our findings suggest that epigenetic accelerated aging, as indicated by Hannum's EEAA, may play a significant role in the increased cancer risk observed in CVE survivors.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"16 1","pages":"135"},"PeriodicalIF":10.4000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583382/pdf/","citationCount":"0","resultStr":"{\"title\":\"Epigenetic age and long-term cancer risk following a stroke.\",\"authors\":\"Antoni Suárez-Pérez, Adrià Macias-Gómez, Isabel Fernández-Pérez, Marta Vallverdú-Prats, Elisa Cuadrado-Godia, Eva Giralt-Steinhauer, Maia Campanale, Daniel Guisado-Alonso, Ana Rodríguez-Campello, Joan Jiménez-Balado, Jordi Jiménez-Conde, Angel Ois\",\"doi\":\"10.1186/s13073-024-01408-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The association between increased cancer risk following a cerebrovascular event (CVE) has been previously reported. We hypothesize that biological age (B-age) acceleration is involved in this association. Our study aims to examine B-age as a novel contributing factor to cancer development post-CVE.</p><p><strong>Methods: </strong>From our prospective stroke registry (BasicMar), we selected 940 cases with epigenetic data. For this study, we specifically analyzed 648 of these patients who had available data, no prior history of cancer, and a minimum follow-up of 3 months. The primary outcome was cancer incidence. B-age was estimated using DNA methylation data derived from whole blood samples obtained within 24 h of stroke onset, employing various epigenetic clocks (including Hannum, Horvath, PhenoAge, Zhang<sub>BLUP</sub>, Zhang<sub>EN</sub>, and the mitotic epiTOC). Extrinsic epigenetic age acceleration (EEAA) was calculated as the residuals from the regression of B-age against chronological age (C-age). For epiTOC, the age-adjusted values were obtained by regressing out the effect of age from the raw epiTOC measurements. Estimated white cell counts were derived from DNA methylation data, and these cell fractions were used to compute the intrinsic epigenetic age acceleration (IEAA). Subsequently, we evaluated the independent association between EEAA, IEAA, and cancer incidence while controlling for potential confounding variables.</p><p><strong>Results: </strong>Among 648 patients with a median follow-up of 8.15 years, 83 (12.8%) developed cancer. Cox multivariable analyses indicated significant associations between Hannum, Zhang, and epiTOC EEAA and the risk of cancer after CVE. After adjusting for multiple testing and competing risks, EEAA measured by Hannum clock maintained an independent association with cancer risk. Specifically, for each year increase in Hannum's EEAA, we observed a 6.0% increased incidence of cancer (HR 1.06 [1.02-1.10], p value = 0.002).</p><p><strong>Conclusions: </strong>Our findings suggest that epigenetic accelerated aging, as indicated by Hannum's EEAA, may play a significant role in the increased cancer risk observed in CVE survivors.</p>\",\"PeriodicalId\":12645,\"journal\":{\"name\":\"Genome Medicine\",\"volume\":\"16 1\",\"pages\":\"135\"},\"PeriodicalIF\":10.4000,\"publicationDate\":\"2024-11-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583382/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genome Medicine\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13073-024-01408-2\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome Medicine","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13073-024-01408-2","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

背景:以前曾有报道称,脑血管事件(CVE)发生后癌症风险增加。我们假设生物年龄(B-age)加速与这种关联有关。我们的研究旨在将 B 年龄作为导致 CVE 后癌症发生的一个新因素进行研究:方法:我们从前瞻性中风登记处(BasicMar)选取了 940 例具有表观遗传学数据的病例。在本研究中,我们特别分析了其中的 648 例患者,这些患者均有可用数据,既往无癌症病史,且随访时间至少为 3 个月。主要结果是癌症发病率。我们利用中风发病 24 小时内采集的全血样本中的 DNA 甲基化数据,采用各种表观遗传时钟(包括 Hannum、Horvath、PhenoAge、ZhangBLUP、ZhangEN 和有丝分裂 epiTOC)估算 B 年龄。外在表观遗传年龄加速度(EEAA)是根据 B 年龄与年代年龄(C 年龄)的回归残差计算得出的。对于表观遗传年龄加速度(epiTOC),年龄调整值是通过从原始表观遗传年龄加速度(epiTOC)测量值中剔除年龄的影响而得到的。估计的白细胞数来自 DNA 甲基化数据,这些细胞分数用于计算内在表观遗传年龄加速度(IEAA)。随后,我们评估了EEAA、IEAA和癌症发病率之间的独立关联,同时控制了潜在的混杂变量:在中位随访 8.15 年的 648 名患者中,83 人(12.8%)罹患癌症。Cox 多变量分析表明,Hannum、Zhang 和 epiTOC EEAA 与 CVE 后的癌症风险有显著关联。在对多重测试和竞争风险进行调整后,Hannum时钟测量的EEAA与癌症风险保持独立关联。具体来说,Hannum的EEAA每增加一年,我们观察到癌症发病率增加6.0%(HR 1.06 [1.02-1.10],P值 = 0.002):我们的研究结果表明,汉纳姆 EEAA 所显示的表观遗传加速衰老可能是导致 CVE 幸存者癌症风险增加的重要原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epigenetic age and long-term cancer risk following a stroke.

Background: The association between increased cancer risk following a cerebrovascular event (CVE) has been previously reported. We hypothesize that biological age (B-age) acceleration is involved in this association. Our study aims to examine B-age as a novel contributing factor to cancer development post-CVE.

Methods: From our prospective stroke registry (BasicMar), we selected 940 cases with epigenetic data. For this study, we specifically analyzed 648 of these patients who had available data, no prior history of cancer, and a minimum follow-up of 3 months. The primary outcome was cancer incidence. B-age was estimated using DNA methylation data derived from whole blood samples obtained within 24 h of stroke onset, employing various epigenetic clocks (including Hannum, Horvath, PhenoAge, ZhangBLUP, ZhangEN, and the mitotic epiTOC). Extrinsic epigenetic age acceleration (EEAA) was calculated as the residuals from the regression of B-age against chronological age (C-age). For epiTOC, the age-adjusted values were obtained by regressing out the effect of age from the raw epiTOC measurements. Estimated white cell counts were derived from DNA methylation data, and these cell fractions were used to compute the intrinsic epigenetic age acceleration (IEAA). Subsequently, we evaluated the independent association between EEAA, IEAA, and cancer incidence while controlling for potential confounding variables.

Results: Among 648 patients with a median follow-up of 8.15 years, 83 (12.8%) developed cancer. Cox multivariable analyses indicated significant associations between Hannum, Zhang, and epiTOC EEAA and the risk of cancer after CVE. After adjusting for multiple testing and competing risks, EEAA measured by Hannum clock maintained an independent association with cancer risk. Specifically, for each year increase in Hannum's EEAA, we observed a 6.0% increased incidence of cancer (HR 1.06 [1.02-1.10], p value = 0.002).

Conclusions: Our findings suggest that epigenetic accelerated aging, as indicated by Hannum's EEAA, may play a significant role in the increased cancer risk observed in CVE survivors.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信