Body composition and the obesity paradox in clear cell renal cell carcinoma

透明细胞肾细胞癌的身体成分和肥胖悖论

• 批准号: 10453737
• 负责人: Anna Helena Furberg-Barnes
• 金额: $ 63.23万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453737
• 关键词: Accounting; Address; Adipose tissue; Affect; Age; American Society of Clinical Oncology; Archives; Area; Behavior Therapy; Behavioral; Biological; Biological Process; Body Composition; Body Size; Body Weight; Body mass index; Body measure procedure; Cancer Patient; Cancer Survivorship; Clear cell renal cell carcinoma; Clinical; Colorectal Cancer; Data; Development; Disease; Fatty acid glycerol esters; Future; Gene Chips; Gene Expression; Genes; Genetic Transcription; Guidelines; Immune; Immune system; Immunologics; Immunotherapy; Incidence; Inflammatory; Intervention; Intuition; Link; Longterm Follow-up; Malignant Neoplasms; Measurement; Mediating; Memorial Sloan-Kettering Cancer Center; Messenger RNA; Metabolic; Metabolic Diseases; Metastatic to; Modeling; Molecular; Molecular Epidemiology; Muscle; Nephrectomy; Nonmetastatic; Nutritional; Obesity; Obesity Epidemic; Operative Surgical Procedures; Outcome; Pathway interactions; Patients; Pharmacological Treatment; Pharmacology; Population; Positioning Attribute; Prognosis; Prognostic Factor; Recommendation; Renal carcinoma; Research; Research Personnel; Risk; Risk Factors; Scanning; Skeletal Muscle; Smoking; Specimen; Time; Tissues; Tumor Markers; Tumor Subtype; Tumor-infiltrating immune cells; Up-Regulation; Visceral; Weight; X-Ray Computed Tomography; base; cancer epidemiology; clinically relevant; comorbidity; density; design; disease heterogeneity; energy balance; epidemiology study; high body mass index; improved; individual patient; insight; molecular scale; molecular subtypes; mortality; mortality risk; novel; novel strategies; patient population; patient subsets; predict clinical outcome; premature; prognostic model; response; risk prediction model; sex; strength training; subcutaneous; tertiary prevention; therapy design; transcriptomics; treatment response; treatment trial; tumor; urologic

ABSTRACT Clear cell renal cell carcinoma (ccRCC) is the most lethal urologic malignancy and its incidence is increasing. The proposed molecular epidemiology study moves beyond body mass index (BMI) to identify ccRCC patients at risk of poor prognosis while considering molecular tumor subtype based on gene expression, and is in direct response to an ASCO position statement that calls for more obesity-related research to ultimately inform weight recommendations and refine prognostic factors for cancer patients. The inverse association between BMI and mortality that is consistently observed among ccRCC patients presents a significant clinical challenge for patients, clinicians, and researchers because it is not clear how to interpret it. Mechanisms underlying the obesity paradox remain largely unexplored. In the proposed study, we will derive new body composition variables from existing, pre-surgical computed tomography (CT) scans, and transcriptomically-characterize the archived tumor specimens from 1200 non-metastatic ccRCC patients who were treated by nephrectomy at Memorial Sloan Kettering Cancer Center between 1995-2017 and followed for clinical outcomes. Based on strong preliminary data we hypothesize that the obesity paradox is influenced by disease heterogeneity and specific body composition features including low skeletal muscle and visceral adipose tissue radiodensity. In Aim 1 we will examine how body composition variables (i.e., area and density of skeletal muscle and adipose tissues) are associated with BMI and with validated ccRCC molecular tumor subtypes that are strongly associated with prognosis. In Aim 2 we will identify which aspects of body composition are independently associated with survival after accounting for molecular tumor subtype. By exploring how tumor RNA expression of immunologic, inflammatory, angiogenic and other cancer-related genes differ by body composition and survival in Aim 3, we will not only further our understanding of the link between body size and biological processes, but may also identify novel targets for tertiary prevention studies. The proposed research has the potential to make a lasting impact on the fields of cancer epidemiology and survivorship by clarifying the clinical interpretation of the obesity paradox, identifying novel prognostic factors derived from readily available CT scans, and informing the development of future behavioral or pharmacological interventions designed to improve clinical outcomes for the growing population of ccRCC patients.

摘要