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: 10474360
• 负责人: Jennifer Wright Bea
• 金额: $ 33.85万
• 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 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10474360
• 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; 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; prognostic indicator; 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 按 BMI（体重/身高2）分类的肥胖与至少 12 种癌症的较高风险相关 绝经后妇女。然而，BMI 是了解身体成分病因学的一个特别生硬的工具 对癌症风险的贡献，并实际确定干预和癌症预防的因果目标。这是 因为 BMI 并没有解决肥胖与癌症关联的核心假设——体重指数越高 腹部内脏脂肪组织（VAT）的水平，在绝经后会更大程度地积累 腹腔内，通过其在炎症中的作用驱动肥胖相关癌症的病理生理学， 代谢和免疫功能障碍——癌症的标志。而皮下的脂肪组织 （皮下，SAT）甚至可能是良性的。 BMI 也无法区分脂肪和肌肉（即瘦肉软肉） 组织，LST），它有可能改善这些 VAT 驱动途径的功能障碍。尽管如此， 肌肉与肿瘤发生的关系尚未得到研究，尽管它正在成为一个重要的组成部分 的生存。尽管与肥胖相关的癌症有所增加，并且三角测量的研究不断涌现，以告知 致癌增值税假说，该假说实际上未经检验。这一建议具有特殊意义 因为证据基础缺乏足够有力的研究来检查详细的身体 成分和人体测量暴露同时与癌症发病率和死亡率相关。这 反映了历史上与测量特定物质相关的高昂成本、可用性和辐射暴露 通过 CT 和 MRI 观察腹部脂肪组织库。双能 X 射线吸收测定法的最新进展 (DXA) 技术经过 CT 和 MRI 验证，使我们能够量化腹部 VAT 和 SAT 女性健康倡议 (WHI) 中现有的 DXA 扫描。我们将类似地测量 腹部 LST，以补充可用的全身测量，在这个近 11,000 人的前瞻性队列中 在基线以及 3、6 和 9 年后重复进行 DXA 测量的女性。我们将研究水平如何 腹部 VAT、SAT 和 LST 以及全身成分和人体测量学与肥胖相关 相关的癌症发病率和死亡率。此外，我们将检查这些身体成分测量 与肺癌的关系（不属于肥胖相关），以解决文献中的异常情况，即 BMI 与肺癌的（负相关）和腰围（正相关）。我们假设增值税，在其他情况下 组织，是所有癌症的危险因素。这个完全独特的数据集具有超过 25 年的裁决结果，将 为上述腹部脂肪组织库和 LST 的病因学作用提供新的见解 癌症风险和癌症死亡率。我们将使用全面、严格的分析方法来解决我们的问题 目标和假设。该研究将为临床实践提供信息并改变其超出预期的影响 我们的目标预示着结果。总之，我们将解决临床和临床方面的主要知识差距