Metabolic health phenotype, accelerated aging and obesity-related cancer risk and mortality

代谢健康表型、加速衰老和肥胖相关的癌症风险和死亡率

• 批准号: 10305540
• 负责人: Prasoona Karra
• 金额: $ 3.44万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10305540
• 关键词: Abdomen; Address; Age; Aging; Atlases; Biological; Biological Aging; Biological Markers; Biometry; Blood; Blood Pressure; Body Weight; Body Weight decreased; Body mass index; Cancer Control; Cancer Patient; Cancer Prevention Intervention; Cancer Prognosis; Cancer Survivor; Cardiometabolic Disease; Cardiovascular Diseases; Categories; Cells; Cessation of life; Characteristics; Chronic; Clinical; Clinical Management; Colorectal; DNA Methylation; Data; Diabetes Mellitus; Diagnosis; Disease; Epidemiology; Epigenetic Process; Esophagus; Etiology; Fatty acid glycerol esters; Female; Framingham Heart Study; Gallbladder; Goals; Health; Health and Retirement Study; High Density Lipoprotein Cholesterol; Homeostasis; Human; Incidence; Individual; Institutes; Intervention; Jackson Heart Study; Lead; Link; Liver; Longevity; Malignant Neoplasms; Measures; Mediating; Mediation; Metabolic; Metabolic dysfunction; Metabolic syndrome; Metabolism; Modification; Multiple Myeloma; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obesity associated cancer; Operative Surgical Procedures; Ovary; Overweight; Pancreas; Participant; Patients; Phase; Phenotype; Physical Function; Play; Postdoctoral Fellow; Premature aging syndrome; Prevalence; Prevention; Process; Public Health; Quality of life; Race; Renal carcinoma; Research; Research Personnel; Risk; Role; Stomach; Testing; The Cancer Genome Atlas; Thinness; Thyroid Gland; Time; Training; Triglycerides; United States; Universities; Utah; Uterus; Women' s Health; bariatric surgery; base; cancer diagnosis; cancer genomics; cancer risk; cancer survival; cancer type; career; cell injury; cohort; diabetes risk; disorder prevention; disorder risk; epidemiology study; fasting glucose; follow-up; high risk; improved outcome; male; malignant breast neoplasm; medical schools; meningioma; mortality; obesity risk; population based; pre-doctoral; prevent; prospective; resilience; response; risk stratification; sex; subcutaneous; waist circumference

PROJECT SUMMARY Obesity-related cancers, type 2 diabetes mellitus and cardiovascular disease, are characterized by a chronic breakdown in metabolic functioning that impacts quality of life, physical functioning and longevity. Though obesity plays a pivotal role in the etiology of at least 13 cancer types, the traditional metric for measuring obesity, body mass index (BMI), is imperfect and may fail to identify a third of individuals at risk of these cancers owing to metabolic dysfunction. While accumulated cellular damage and abrogated resilience mechanisms are part of the natural aging process, damage accumulation and dysregulation of homeostasis mechanisms, potentially driven by metabolic dysfunction, may lead to accelerated biological aging that has recently been linked to cancer risk and survival. A better understanding of the relationship between metabolic health, regardless of BMI, with accelerated aging and cancer is needed to inform who to target for prevention efforts. The long-term goal of this application is to understand how metabolic dysfunction influences biological aging and risk of cancer, at all levels of adiposity, to inform interventions that prevent or delay these deadly diseases. The central hypothesis is that metabolic dysfunction, independent of obesity, is associated with accelerated biological aging and obesity-related cancers. Aim 1 (F99 phase) will leverage data from the Utah Obesity Study to measure the association between metabolic dysfunction (metabolic syndrome and diabetes) across BMI categories (i.e., “metabolic health phenotype”) and risk of developing obesity-related cancer (esophageal, gastric, colorectal, liver, gallbladder, pancreas, uterus, ovary, thyroid, meningioma, kidney, and breast cancers, and multiple myeloma). In the Women’s Health Initiative (WHI), diabetes status at cancer diagnosis will be measured in relation to cancer-specific and overall survival. This research will be extended in Aim 2 (K00 phase) where metabolic health phenotype will be studied in relation to accelerated biological aging and obesity-related cancer risk. In Aim 2a, data from the prospective WHI, Jackson Heart Study, Health and Retirement Study, Framingham Heart Study and others will be used to measure the extent to which accelerated biological age explains the association of metabolic health phenotype with obesity-related cancer risk. In Aim 2b, using data from The Cancer Genomic Atlas (TCGA) cohort, accelerated biological aging will be evaluated in relation to survival after obesity-related cancer diagnosis. The pre-doctoral to post-doctoral candidate will expand upon her didactic and experiential training in biostatistics, epidemiology, aging and epigenetics research both at the University of Utah, Huntsman Cancer Institute, and Yale School of Medicine. Practical training will be obtained in human metabolism, biostatistics, epidemiology, aging and epigenetics research. The proposed project will help to better identify those at risk of obesity-related cancers and support changes in clinical cancer management to support diabetes and accelerated aging prevention.

项目摘要 肥胖相关癌症，2型糖尿病和心血管疾病的特征是慢性 代谢功能的细分，会影响生活质量，身体功能和寿命。尽管 肥胖症在至少13种癌症类型的病因中起关键作用，这是用于测量的传统指标 肥胖，体重指数（BMI）是不完美的，可能无法识别出有风险的三分之一的人 癌症由于代谢功能障碍。而累积的细胞损伤和消除的弹性 机制是自然衰老过程的一部分，损害积累和体内稳态失调 可能由代谢功能障碍驱动的机制可能会导致生物衰老加速 最近与癌症风险和生存有关。更好地理解代谢之间的关系 无论BMI如何，健康都需要加速衰老和癌症，以告知谁针对预防 努力。该应用的长期目标是了解代谢功能障碍如何影响生物学 衰老和癌症的风险，以各种肥胖水平，以告知预防或延迟这些致命的干预措施 疾病。中心假设是，与肥胖无关的代谢功能障碍与 加速生物衰老和与肥胖相关的癌症。 AIM 1（F99阶段）将利用犹他州的数据 肥胖研究以测量代谢功能障碍（代谢综合征和糖尿病）之间的关联 跨BMI类别（即“代谢健康表型”）和患肥胖相关癌症的风险 （食管胃结直肠肝胆囊胰腺子宫子宫甲状腺脑膜瘤肾脏和 乳腺癌和多发性骨髓瘤）。在妇女健康计划（WHI）中，癌症的糖尿病状况 诊断将与癌症特异性和总体生存有关。这项研究将扩展 AIM 2（K00期），代谢健康表型将与加速生物衰老有关 和与肥胖相关的癌症风险。在AIM 2A中，来自潜在WHI，杰克逊心脏研究，健康和的数据 退休研究，弗雷明汉心脏研究和其他人将被用来衡量的程度 加速生物年龄解释了代谢健康表型与肥胖相关癌症的关联 风险。在AIM 2B中，使用来自癌症基因组图集（TCGA）队列的数据，将加速生物老化 与肥胖相关癌症诊断后的生存评估。博士后博士后 候选人将扩大她在生物统计学，流行病学，衰老和 犹他大学，亨斯曼癌症研究所和耶鲁大学医学院的表观遗传学研究。 将在人类代谢，生物统计学，流行病学，衰老和表观遗传学中获得实践培训 研究。拟议的项目将有助于更好地识别有肥胖相关癌症风险的人并支持 临床癌症管理的变化，以支持糖尿病和加速预防衰老。