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

抽象的 由BMI分类（体重/高度2）分类的肥胖症与至少12种癌症的风险相关 绝经后妇女。但是，BMI是理解身体组成的病因的特别钝工具 对癌症风险的贡献，实际上确定了用于干预和预防癌症的因果目标。这是 因为BMI并未解决肥胖症协会基础的核心假设 - 较高 腹部内脏脂肪组织（VAT）的水平，在更年期后积累 腹腔内腔，通过其在炎症中的作用来驱动与肥胖相关的癌症的病理生理学， 代谢和免疫功能障碍 - 癌症的标志。而脂肪组织在皮肤下方 （皮下）甚至可能是良性的。 BMI也不会在脂肪和肌肉之间描绘 组织，LST），它有可能在这些增值税驱动的途径中改善功能障碍。尽管如此， 尽管肌肉作为重要组成部分，但尚未与肿瘤发生有关 生存。尽管与肥胖相关的癌症和迅速研究的研究有所增加，以告知三角研究 致癌性增值税假说，该假设实际上未经测试。该提议特别重要 因为证据基础缺乏能够检查两个详细身体的足够动力的研究 与癌症发生率和死亡率相关的组成和人体测量学暴露。这 反映与测量特定相关的历史成本，可用性和辐射暴露 CT和MRI腹部脂肪组织库。双能X射线吸收法的最新进展 （DXA）针对CT和MRI进行了验证的技术使我们能够量化腹部增值税并从 现有的DXA扫描在良好的妇女健康计划（WHI）中。我们将同样衡量 腹部LST，以补充可用的总体措施，在这个前瞻性队列中 在基线和3，6年后进行DXA测量的妇女在9年后进行了重复测量。我们将研究如何水平 腹部桶，SAT和LST以及全身成分和人体测量法，与肥胖相关 相关的癌症发病率和死亡率。此外，我们将检查这些身体组成措施 与肺癌（不归类为肥胖相关）的关系，以解决文献中的异常情况，即BMI （逆）和腰部（阳性）与肺癌的关联。我们假设该增值税，在其他情况下 对于所有癌症，组织是危险因素。这个完全独特的数据集，具有25年以上的裁决结果 提供有关上述腹部脂肪组织和LST的病因作用的新见解 在癌症风险和癌症死亡率中。我们将使用一种全面，严格的分析方法来解决我们的 目的和假设。该研究将为临床实践提供信息，超出预期的影响 我们的目标portend的结果。总而言之，我们将解决临床和