Adipose and Lean Soft Tissue Depots, Cancer Risk and Mortality in Postmenopausal Women

绝经后妇女的脂肪和瘦肉软组织库、癌症风险和死亡率

• 批准号: 10207559
• 负责人: Jennifer Wright Bea
• 金额: $ 34.58万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207559
• 关键词: Abdomen; Abdominal Cavity; Abdominal Muscles; Accounting; Address; Adipose tissue; Age; Aging; Anthropometry; Behavior; Benign; Body Composition; Body Weight; Body fat; Body mass index; Body measure procedure; Cancer Control; Cancer Patient; Cessation of life; Clinic; Clinical; Colorectal Cancer; Complement; Computer software; Data; Data Set; Deposition; Dual-Energy X-Ray Absorptiometry; Etiology; Event; Fatty acid glycerol esters; Functional disorder; Habits; Immune System Diseases; Incidence; Inflammation; Inflammatory; Intervention; Intra-abdominal; Investigation; Knowledge; Life Style; Literature; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Measures; Metabolic dysfunction; Modality; Muscle; Obesity; Obesity associated cancer; Outcome; Pathway interactions; Positioning Attribute; Postmenopause; Prognostic Marker; Prospective cohort; Public Health; Radiation; Radiation exposure; Research; Risk; Risk Assessment; Risk Factors; Role; Sample Size; Scanning; Skeletal Muscle; Skin; Smoking; Smoking Status; Sum; Technology; Testing; Thinness; Time; Tissues; Visceral; Woman; Women' s Health; X-Ray Computed Tomography; adjudicate; base; cancer prevention; cancer risk; cancer subtypes; carcinogenicity; clinical practice; cohort; cost; evidence base; experience; follow-up; high risk; immune function; improved; innovation; insight; longitudinal dataset; malignant breast neoplasm; mortality; mortality risk; new technology; novel; prospective; research study; soft tissue; subcutaneous; tool; tumorigenesis; waist circumference

ABSTRACT Obesity, classified by BMI (body weight/height2) is associated with higher risk of at least 12 cancers in postmenopausal women. Yet, BMI is a particularly blunt tool to understand the etiology of body composition contributions to cancer risk, and actually identify causal targets for intervention and cancer prevention. This is because BMI does not address the central hypothesis underlying the obesity-cancer association- that higher levels of abdominal visceral adipose tissue (VAT), which accumulates to a greater extent post menopause in the intra-abdominal cavity, drives the pathophysiology of obesity-related cancers via its role in inflammatory, metabolic, and immune dysfunction - hallmarks of cancer. Whereas adipose tissue just under the skin (subcutaneous, SAT) may even be benign. BMI also does not delineate between fat and muscle (i.e. lean soft tissue, LST), which has the potential to ameliorate dysfunction in these VAT driven pathways. Nevertheless, muscle has not been examined in relation to tumorigenesis, though it is emerging as an important component of survival. Despite the increase in obesity-related cancers and burgeoning research triangulated to inform the carcinogenic VAT hypothesis, the hypothesis is effectively untested. This proposal is of particular significance because the evidence base lacks sufficiently powered studies that are able to examine both detailed body composition and anthropometric exposures simultaneously in relation to cancer incidence and mortality. This reflects the historical prohibitive cost, availability, and radiation exposure associated with measuring specific abdominal adipose tissue depots by CT and MRI. Recent advances in Dual Energy X-Ray Absorptiometry (DXA) technology, validated against CT and MRI, have allowed us to quantify abdominal VAT and SAT from existing DXA scans within the well-characterized Women's Health Initiative (WHI). We will similarly measure abdominal LST, to complement the total body measures available, in this prospective cohort of nearly 11,000 women with repeated DXA measurements at baseline and 3, 6 and 9 years later. We will examine how levels of abdominal VAT, SAT and LST, as well as total body composition and anthropometry, associate with obesity- related cancer incidence and mortality. Moreover, we will examine these body composition measures in relation to lung cancer, (not classified as obesity-related) to address anomalies in the literature, i.e. BMI (inverse) and waist (positive) associations with lung cancer. We hypothesize that VAT, in the context of other tissues, is a risk factor, for all cancers. This wholly unique dataset with adjudicated outcomes over 25 years will provide novel insight into the etiological role of the aforementioned abdominal adipose tissue depots and LST in cancer risk and cancer mortality. We will use a comprehensive, rigorous analytic approach to address our aims and hypotheses. The study will inform and alter clinical practice beyond the anticipated impact that the results from our aims portend. In sum, we will address a major knowledge gap of both clinical and

摘要