Domingo-Relloso Arce, Riffo-Campos Angela L, Zhao Naisi, Ayala Guillermo, Haack Karin, Manterola Carlos, Rhoades Dorothy A, Umans Jason G, Fallin M Daniele, Herreros-Martinez Miguel, Pollan Marina, Boerwinkle Eric, Platz Elizabeth A, Jones Miranda R, Bressler Jan, Joehanes Roby, Ryan Calen P, Gonzalez Juan R, Levy Daniel, Belsky Daniel W, Cole Shelley A, Michaud Dominique S, Navas-Acien Ana, Tellez-Plaza Maria
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York, USA.
Integrative Epidemiology Group, National Center for Epidemiology, Instituto de Salud Carlos III, Madrid, Spain.
JACC CardioOncol. 2024 Sep 10;6(5):731-742. doi: 10.1016/j.jaccao.2024.07.014. eCollection 2024 Oct.
Emerging evidence reveals a complex relationship between cardiovascular disease (CVD) and cancer, which share common risk factors and biological pathways.
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.
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.
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.
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.
新出现的证据揭示了心血管疾病（CVD）与癌症之间的复杂关系，二者具有共同的风险因素和生物学途径。
本研究旨在评估来自3个不同种族队列中CVD和癌症发病率的常见表观遗传特征：来自SHS（强心研究）的美国原住民、来自FHS（弗雷明汉心脏研究）的欧裔美国人，以及来自ARIC（社区动脉粥样硬化风险）研究的欧裔美国人和非裔美国人。
采用两阶段策略，首先对每个队列进行非靶向全表观基因组关联研究，然后在已识别的差异甲基化位点（DMP）的联合集中运行靶向模型。我们还通过生物信息学分析探索潜在的分子途径。
在所有人群中均识别出常见的DMP。在随后的荟萃分析中，这些DMP中有3个和1个分别仅对CVD以及对癌症和CVD均具有统计学意义。没有经荟萃分析的DMP仅对癌症具有统计学意义。富集分析指出了癌症和CVD中涉及的相互关联的生物学途径。在DrugBank数据库中，与一碳代谢以及癌症和CVD药物相关的元素被识别为靶基因产物的潜在药物。在一项仅限于950名发生新发CVD的SHS参与者的额外分析中，当针对在其他队列中识别出的联合癌症和CVD的DMP调整模型时，新发癌症的C指数从0.618（95%CI：0.570 - 0.672）增至0.971（95%CI：0.963 - 0.978）。
这些结果指出了用于精准预防CVD和癌症的分子途径及潜在治疗方法。基于新发CVD和癌症的常见表观遗传特征进行筛查可能有助于识别癌症风险增加的新诊断CVD患者。
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