Proteomic aging in adults before and after cancer diagnosis

癌症诊断前后成人的蛋白质组老化

• 批准号: 10661835
• 负责人: Anna Prizment
• 金额: $ 34.17万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10661835
• 关键词: Acceleration; Adult; Age; Aging; Agreement; Area; Atherosclerosis Risk in Communities; Biological; Biological Aging; Biological Assay; Biological Markers; Black race; Blood; Body mass index; Cancer Detection; Cancer Etiology; Cancer Survivor; Cause of Death; Cessation of life; Characteristics; Chronic; Chronology; Clinical; Cognitive; Consensus; Data; Deceleration; Development; Diagnosis; Disease; Education; Epigenetic Process; Exclusion; Future; Immune response; Individual; Inflammation; Intervention; Knowledge; Life Style; Malignant Neoplasms; Measurement; Measures; Metformin; Morbidity - disease rate; Multi-Ethnic Study of Atherosclerosis; Obesity associated cancer; Outcome; Participant; Performance; Persons; Pharmaceutical Preparations; Physiological; Plasma Proteins; Premature Mortality; Proteins; Proteomics; Public Health; Publishing; Race; Recording of previous events; Research; Research Personnel; Residual Cancers; Residual state; Risk; Risk Factors; Role; Screening for cancer; Site; Smoking; Supervision; Survival Rate; Survivors; Testing; Time; Training; Validation; Visit; Woman; Work; age related; anti aging; biomarker identification; cancer diagnosis; cancer risk; cancer site; cancer survival; cancer therapy; cancer type; clinically significant; cohort; cost efficient; experience; frailty; improved; indexing; men; mortality; novel; novel strategies; population based; prospective; risk stratification; sex; sex risk; tool; transcriptomics

PROJECT SUMMARY Cancer survivors experience age-related diseases at earlier age than cancer-free persons, suggesting that cancer survivors have accelerated aging. Accelerated aging among cancer survivors could be caused by cancer treatment, but it could also be related to immune response and chronic inflammation. Chronic inflammation is also found in individuals who subsequently develop cancer with subsequent risk of cancer development, and it is possible that accelerated aging starts even before cancer diagnosis. To assess biological aging before and after cancer diagnosis, we will use existing proteomic data and construct and validate proteomic aging clocks in the prospective population-based Atherosclerosis Risk in the Community (ARIC) cohort. The proteins have been already measured three times over 20 years using highly sensitive SomaScan assay. The proteomic aging clocks will be externally validated in the Multi-Ethnic Study of Atherosclerosis (MESA). The strengths of proteomic aging clocks are that these clocks are easily measured, accurately predict biological aging, and are associated with age-related diseases and mortality. However, it is unknown whether proteomic aging clocks predict cancer risk or outcomes in cancer survivors, and there is no agreement about the optimal clock in the context of cancer. To overcome this gap in knowledge, we will construct and validate proteomic aging clocks in ARIC participants who are cancer free but may have other conditions, i.e. these clocks will be cancer-specific proteomic aging clocks (so called, CaPACs). In addition, we will examine the previously published and validated proteomic aging clocks. Our central hypothesis is that accelerated aging is associated with (1) increased cancer risk in persons who are cancer-free at baseline and (2) premature mortality and morbidity among cancer survivors at middle and later age. In the first aim, we will examine the associations between age acceleration for all CaPACs and the risk of overall cancer and specific cancer types in ARIC and MESA. The associations will be also stratified by sex and race. In the second aim, we will examine associations between age acceleration for all CaPACs and all-cause mortality, mortality from causes other than their index cancer, and frailty among cancer survivors in ARIC. In addition, we will compare associations with mortality among cancer survivors and those without cancer history. The use of existing data from the ARIC and MESA studies will allow for quick and cost-efficient testing of our hypothesis. The quantification of proteomic aging in cancer is clinically important because the knowledge of biological age will not only inform risk-stratified cancer screening and post-diagnosis cancer surveillance, but also facilitate the development of anti-aging drugs. 1

项目总结 癌症幸存者比没有癌症的人更早患上与年龄相关的疾病，这表明 癌症幸存者加速了衰老。癌症幸存者加速衰老可能是由 癌症治疗，但它也可能与免疫反应和慢性炎症有关。慢性 随后罹患癌症并有罹患癌症风险的人也会出现炎症。 而且，加速衰老甚至可能在癌症诊断之前就开始了。评估 在癌症诊断之前和之后的生物老化，我们将利用现有的蛋白质组数据和构建 在社区以人群为基础的动脉粥样硬化风险中验证蛋白质组衰老时钟 (ARIC)队列。在过去的20年里，这些蛋白质已经被用高度敏感的仪器测量了三次。 SomaScan分析。蛋白质组衰老时钟将在多种族研究中得到外部验证 动脉粥样硬化(MESA)。蛋白质组衰老时钟的优点是这些时钟很容易测量， 准确预测生物衰老，并与年龄相关的疾病和死亡率相关。然而，它是 目前尚不清楚蛋白质组衰老时钟是否可以预测癌症幸存者的癌症风险或预后，也没有 就癌症背景下的最佳时钟达成一致。为了克服这一知识差距，我们将 在无癌症但可能有其他癌症的ARIC参与者中构建和验证蛋白质组衰老时钟 条件，即这些时钟将是癌症特异的蛋白质组衰老时钟(所谓的，CaPAC)。此外, 我们将检查以前发表和验证的蛋白质组衰老时钟。我们的中心假设是 加速衰老与(1)基线无癌症的人的癌症风险增加有关， (2)癌症存活者中老年过早死亡率和发病率。在第一个目标中，我们将 检查所有CAPAC的年龄加速与总体癌症风险和特定癌症风险之间的关系 ARIC和MESA的癌症类型。这些关联还将按性别和种族分层。在第二个目标中， 我们将检查所有CAPAC的年龄加速与全原因死亡率、 癌症指标以外的其他原因，以及ARIC癌症幸存者的虚弱。此外，我们还将比较 癌症幸存者和那些没有癌症病史的人与死亡率的关系。现有数据的使用 来自ARIC和MESA的研究将允许对我们的假设进行快速且经济高效的检验。这个 癌症中蛋白质组老化的量化具有重要的临床意义，因为生物学年龄的知识将 不仅为癌症风险分层筛查和诊断后癌症监测提供信息，而且还促进 抗衰老药物的开发。 1