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.

项目概要 与肥胖相关的癌症、2 型糖尿病和心血管疾病的特点是慢性 代谢功能崩溃，影响生活质量、身体机能和寿命。尽管 肥胖在至少 13 种癌症的病因学中发挥着关键作用，这是衡量癌症的传统指标 肥胖、体重指数 (BMI) 并不完美，可能无法识别出有这些风险的三分之一的人 由于代谢功能障碍而导致癌症。细胞损伤不断累积并丧失了恢复力 机制是自然衰老过程、损伤积累和体内平衡失调的一部分 可能由代谢功能障碍驱动的机制可能导致生物衰老加速 最近与癌症风险和生存相关。更好地理解新陈代谢之间的关系 无论体重指数如何，加速衰老和癌症的健康状况都需要告知谁是预防的目标 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 衰老和癌症风险，在各个肥胖水平上，为预防或延缓这些致命的干预措施提供信息 疾病。中心假设是代谢功能障碍与肥胖无关，与 加速生物衰老和与肥胖相关的癌症。目标 1（F99 阶段）将利用来自犹他州的数据 肥胖研究测量代谢功能障碍（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、卵巢、甲状腺、脑膜瘤、肾和 乳腺癌和多发性骨髓瘤）。在妇女健康倡议 (WHI) 中，糖尿病与癌症的关系 诊断将根据癌症特异性和总体生存率进行衡量。这项研究将扩展至 目标 2（K00 阶段）将研究代谢健康表型与加速生物衰老的关系 以及与肥胖相关的癌症风险。在目标 2a 中，数据来自前瞻性 WHI、杰克逊心脏研究、健康和 退休研究、弗雷明汉心脏研究等将用于衡量 加速的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。在目标 2b 中，利用癌症基因组图谱 (TCGA) 队列的数据，加速生物衰老将 评估肥胖相关癌症诊断后的生存率。博士前到博士后 候选人将扩展她在生物统计学、流行病学、老龄化和 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。 将获得人体新陈代谢、生物统计学、流行病学、衰老和表观遗传学方面的实践培训 研究。拟议的项目将有助于更好地识别那些有肥胖相关癌症风险的人并提供支持 临床癌症管理的变化以支持糖尿病和加速衰老预防。