Arce Domingo-Relloso PhD , Angela L. Riffo-Campos PhD , Naisi Zhao DrPH , Guillermo Ayala PhD , Karin Haack PhD , Carlos Manterola MD, PhD , Dorothy A. Rhoades MD, MPH , Jason G. Umans MD, PhD , M Daniele Fallin PhD , Miguel Herreros-Martinez MS , Marina Pollan MD, PhD , Eric Boerwinkle PhD , Elizabeth A. Platz ScD, MPH , Miranda R. Jones PhD , Jan Bressler PhD , Roby Joehanes PhD , Calen P. Ryan PhD , Juan R. Gonzalez PhD , Daniel Levy MD , Daniel W. Belsky PhD , Maria Tellez-Plaza MD, PhD
{"title":"全因心血管疾病和癌症发病率的多队列表观基因组关联研究","authors":"Arce Domingo-Relloso PhD , Angela L. Riffo-Campos PhD , Naisi Zhao DrPH , Guillermo Ayala PhD , Karin Haack PhD , Carlos Manterola MD, PhD , Dorothy A. Rhoades MD, MPH , Jason G. Umans MD, PhD , M Daniele Fallin PhD , Miguel Herreros-Martinez MS , Marina Pollan MD, PhD , Eric Boerwinkle PhD , Elizabeth A. Platz ScD, MPH , Miranda R. Jones PhD , Jan Bressler PhD , Roby Joehanes PhD , Calen P. Ryan PhD , Juan R. Gonzalez PhD , Daniel Levy MD , Daniel W. Belsky PhD , Maria Tellez-Plaza MD, PhD","doi":"10.1016/j.jaccao.2024.07.014","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Emerging evidence reveals a complex relationship between cardiovascular disease (CVD) and cancer, which share common risk factors and biological pathways.</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate common epigenetic signatures for CVD and cancer incidence in 3 ethnically diverse cohorts: Native Americans from the SHS (Strong Heart Study), European Americans from the FHS (Framingham Heart Study), and European Americans and African Americans from the ARIC (Atherosclerosis Risk In Communities) study.</div></div><div><h3>Methods</h3><div>A 2-stage strategy was used that included first conducting untargeted epigenome-wide association studies for each cohort and then running targeted models in the union set of identified differentially methylated positions (DMPs). We also explored potential molecular pathways by conducting a bioinformatics analysis.</div></div><div><h3>Results</h3><div>Common DMPs were identified across all populations. In a subsequent meta-analysis, 3 and 1 of those DMPs were statistically significant for CVD only and both cancer and CVD, respectively. No meta-analyzed DMPs were statistically significant for cancer only. The enrichment analysis pointed to interconnected biological pathways involved in cancer and CVD. In the DrugBank database, elements related to 1-carbon metabolism and cancer and CVD medications were identified as potential drugs for target gene products. In an additional analysis restricted to the 950 SHS participants who developed incident CVD, the C index for incident cancer increased from 0.618 (95% CI: 0.570-0.672) to 0.971 (95% CI: 0.963-0.978) when adjusting the models for the combined cancer and CVD DMPs identified in the other cohorts.</div></div><div><h3>Conclusions</h3><div>These results point to molecular pathways and potential treatments for precision prevention of CVD and cancer. Screening based on common epigenetic signatures of incident CVD and cancer may help identify patients with newly diagnosed CVD at increased cancer risk.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"6 5","pages":"Pages 731-742"},"PeriodicalIF":12.0000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multicohort Epigenome-Wide Association Study of All-Cause Cardiovascular Disease and Cancer Incidence\",\"authors\":\"Arce Domingo-Relloso PhD , Angela L. Riffo-Campos PhD , Naisi Zhao DrPH , Guillermo Ayala PhD , Karin Haack PhD , Carlos Manterola MD, PhD , Dorothy A. Rhoades MD, MPH , Jason G. Umans MD, PhD , M Daniele Fallin PhD , Miguel Herreros-Martinez MS , Marina Pollan MD, PhD , Eric Boerwinkle PhD , Elizabeth A. Platz ScD, MPH , Miranda R. Jones PhD , Jan Bressler PhD , Roby Joehanes PhD , Calen P. Ryan PhD , Juan R. Gonzalez PhD , Daniel Levy MD , Daniel W. Belsky PhD , Maria Tellez-Plaza MD, PhD\",\"doi\":\"10.1016/j.jaccao.2024.07.014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Emerging evidence reveals a complex relationship between cardiovascular disease (CVD) and cancer, which share common risk factors and biological pathways.</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate common epigenetic signatures for CVD and cancer incidence in 3 ethnically diverse cohorts: Native Americans from the SHS (Strong Heart Study), European Americans from the FHS (Framingham Heart Study), and European Americans and African Americans from the ARIC (Atherosclerosis Risk In Communities) study.</div></div><div><h3>Methods</h3><div>A 2-stage strategy was used that included first conducting untargeted epigenome-wide association studies for each cohort and then running targeted models in the union set of identified differentially methylated positions (DMPs). We also explored potential molecular pathways by conducting a bioinformatics analysis.</div></div><div><h3>Results</h3><div>Common DMPs were identified across all populations. In a subsequent meta-analysis, 3 and 1 of those DMPs were statistically significant for CVD only and both cancer and CVD, respectively. No meta-analyzed DMPs were statistically significant for cancer only. The enrichment analysis pointed to interconnected biological pathways involved in cancer and CVD. In the DrugBank database, elements related to 1-carbon metabolism and cancer and CVD medications were identified as potential drugs for target gene products. In an additional analysis restricted to the 950 SHS participants who developed incident CVD, the C index for incident cancer increased from 0.618 (95% CI: 0.570-0.672) to 0.971 (95% CI: 0.963-0.978) when adjusting the models for the combined cancer and CVD DMPs identified in the other cohorts.</div></div><div><h3>Conclusions</h3><div>These results point to molecular pathways and potential treatments for precision prevention of CVD and cancer. 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Multicohort Epigenome-Wide Association Study of All-Cause Cardiovascular Disease and Cancer Incidence
Background
Emerging evidence reveals a complex relationship between cardiovascular disease (CVD) and cancer, which share common risk factors and biological pathways.
Objectives
The aim of this study was to evaluate common epigenetic signatures for CVD and cancer incidence in 3 ethnically diverse cohorts: Native Americans from the SHS (Strong Heart Study), European Americans from the FHS (Framingham Heart Study), and European Americans and African Americans from the ARIC (Atherosclerosis Risk In Communities) study.
Methods
A 2-stage strategy was used that included first conducting untargeted epigenome-wide association studies for each cohort and then running targeted models in the union set of identified differentially methylated positions (DMPs). We also explored potential molecular pathways by conducting a bioinformatics analysis.
Results
Common DMPs were identified across all populations. In a subsequent meta-analysis, 3 and 1 of those DMPs were statistically significant for CVD only and both cancer and CVD, respectively. No meta-analyzed DMPs were statistically significant for cancer only. The enrichment analysis pointed to interconnected biological pathways involved in cancer and CVD. In the DrugBank database, elements related to 1-carbon metabolism and cancer and CVD medications were identified as potential drugs for target gene products. In an additional analysis restricted to the 950 SHS participants who developed incident CVD, the C index for incident cancer increased from 0.618 (95% CI: 0.570-0.672) to 0.971 (95% CI: 0.963-0.978) when adjusting the models for the combined cancer and CVD DMPs identified in the other cohorts.
Conclusions
These results point to molecular pathways and potential treatments for precision prevention of CVD and cancer. Screening based on common epigenetic signatures of incident CVD and cancer may help identify patients with newly diagnosed CVD at increased cancer risk.
期刊介绍：
JACC: CardioOncology is a specialized journal that belongs to the esteemed Journal of the American College of Cardiology (JACC) family. Its purpose is to enhance cardiovascular care for cancer patients by publishing high-quality, innovative scientific research and sharing evidence-based knowledge.
The journal aims to revolutionize the field of cardio-oncology and actively involve and educate professionals in both cardiovascular and oncology fields. It covers a wide range of topics including pre-clinical, translational, and clinical research, as well as best practices in cardio-oncology. Key areas of focus include understanding disease mechanisms, utilizing in vitro and in vivo models, exploring novel and traditional therapeutics (across Phase I-IV trials), studying epidemiology, employing precision medicine, and investigating primary and secondary prevention.
Amyloidosis, cardiovascular risk factors, heart failure, and vascular disease are some examples of the disease states that are of particular interest to the journal. However, it welcomes research on other relevant conditions as well.
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