Adiposity and Outcomes of Clinically Localized Prostate Cancer

肥胖和临床局限性前列腺癌的结果

基本信息

批准号：
7998214
负责人：
Vincent L Freeman
金额：
$ 59.25万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-01-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7998214
关键词：
Abdomen Accounting Address Adipose tissue Adult Aftercare Anthropometry Arachidonic Acids Archives Area Behavioral Biochemical Biological Blood Body Composition Body Size Body Weight Body fat Body mass index Cancer Biology Cancer Control Cancer Prognosis Characteristics Chemoprevention Chicago Clinic Clinical Clinical Protocols Clinical assessments Cohort Studies Collection Data Diagnosis Diagnostic Dinoprostone Disease Eicosanoids Enrollment Epidemic Epidemiology Erythrocytes Estrogens Exposure to Failure Fatty Acids Fatty acid glycerol esters Future Gland Gonadal Steroid Hormones Health Health Personnel Health Professional Health behavior Hormonal Human IL8 gene Illinois Imaging Techniques Immunity Immunologic Factors Individual Inflammation Insulin-Like Growth Factor I Insulin-Like Growth-Factor Binding Protein 1 Insulin-Like-Growth Factor I Receptor Interleukin-6 Intervention Kinesiology Leptin Leukocytes Leukotriene B4 Life Style Light Link Malignant neoplasm of prostate Measures Mediating Mediation Mediator of activation protein Medical center Medicine Metabolic Metabolism Modeling Morbidity - disease rate Nutritional Obesity Operative Surgical Procedures Outcome Overweight Pathologic Pathologist Pathology Pathway interactions Patients Periprostatic Pharmaceutical Chemistry Phase Physiological Physiological Processes Plasma Population Positioning Attribute Prevalence Prostate Prostate-Specific Antigen Prostatectomy Prostatic Proteins Public Health Publishing Radical Prostatectomy Receptor Signaling Relative (related person)Research Risk Risk Factors Science Scientist Serum Signal Pathway Signaling Protein Somatomedins Source Specimen Staging Stearic Acids Surgical margins TNF gene Target Populations Testing Testosterone Time Tissues Treatment Factor United States Universities Urology Variant Visceral Weight abdominal fat adiponectin base cancer recurrence cohort cytokine design lifestyle factors man meetings men monocyte mortality nutrition outcome forecast peptide hormone prevent prospective repository tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): This application attempts to clarify the mechanistic basis for the association between excessive adiposity and risk factors for prostate cancer-specific morbidity and mortality in men with clinically localized prostate cancer. The overall hypothesis is that excess adiposity alters prostatic exposure to nutritional, hormonal, and immunologic factors influenced by weight status and implicated in prostate cancer progression, and that inter- individual variation in gland-level exposure to these factors mediates the effects of adiposity on the pathologic presentation and course of the disease. To test this hypothesis, we will: Aim 1) conduct a prospective 2-year cohort study of incident cases of clinically localized prostate cancer to measure the association of adiposity with pathologic tumor features at diagnosis and 2-year risk of biochemical (PSA) failure after radical prostatectomy; Aim 2) measure fatty acids, insulin-like growth factor (IGF) axis activity, modulators of inflammation, and sex steroid hormone profiles in prostate tissue and periprostatic fat collected at surgery, and use mediation model analysis to determine which physiologic variables account for the effects adiposity on tumor characteristics and risk of biochemical failure; Aim 3) and evaluate the effects of post-treatment changes in adiposity on 2-year risk of biochemical failure. The cohort will consist of 540 men enrolled in the urology clinics of four Chicago-area medical centers who are awaiting prostatectomy for clinically localized prostate cancer. Adiposity will be quantified by anthropometry and dual energy x-ray absorptiometry at diagnosis and one year after surgery. Pathologic tumor characteristics will be determined by a single pathologist, and biochemical outcomes will be ascertained using a standard clinical protocol. Potential mediators to be studied include fatty acids, the IGF-1 receptor signaling pathway, adipose tissue-derived cytokines, eicosanoids products of arachidonic acid, and metabolites of estrogen and testosterone. Lifestyle factors that associate with more rapid progression of clinically early-stage prostate cancer are of increasing concern to health care providers and public health professionals. This research, to be completed over 5 years, will identify some of the biological reasons why obesity associates with more "aggressive" prostate cancer at diagnosis and decreases a man's chances for cure with surgery. It will also shed light on ways to prevent prostate cancer recurrence that may involve new or existing medicines or lifestyle changes. PUBLIC HEALTH RELEVANCE: Lifestyle factors that associate with more rapid progression of clinically early-stage prostate cancer are of increasing concern to health care providers and public health professionals. This research, to be completed over 5 years, will identify some of the biological reasons why obesity associates with more "aggressive" prostate cancer at diagnosis and decreases a man's chances for cure with surgery. It will also shed light on ways to prevent prostate cancer recurrence that may involve new or existing medicines or lifestyle changes.

描述（由申请人提供）：本申请试图阐明临床局限性前列腺癌男性中过度肥胖与前列腺癌特异性发病率和死亡率的危险因素之间关联的机制基础。总体假设是，过度肥胖会改变前列腺对营养、激素和免疫因素的暴露，这些因素受体重状况影响，并与前列腺癌的进展有关，并且腺体水平暴露于这些因素的个体间差异介导了肥胖对前列腺癌的影响。病理表现和病程。为了检验这一假设，我们将：目标 1) 对临床局限性前列腺癌的发病病例进行一项为期 2 年的前瞻性队列研究，以测量肥胖与诊断时肿瘤病理特征以及 2 年生化 (PSA) 失败风险之间的关系根治性前列腺切除术后；目标 2) 测量手术时收集的前列腺组织和前列腺周围脂肪中的脂肪酸、胰岛素样生长因子 (IGF) 轴活性、炎症调节剂和性类固醇激素谱，并使用中介模型分析来确定哪些生理变量可解释肥胖对肿瘤特征和生化失败风险的影响；目标 3) 并评估治疗后肥胖变化对 2 年生化失败风险的影响。该队列将由 540 名在芝加哥地区四个医疗中心的泌尿科诊所登记的男性组成，他们正在等待因临床局限性前列腺癌接受前列腺切除术。在诊断时和手术后一年，将通过人体测量学和双能 X 射线吸收测量法对肥胖进行量化。肿瘤病理特征将由一位病理学家确定，生化结果将使用标准临床方案确定。需要研究的潜在介质包括脂肪酸、IGF-1 受体信号通路、脂肪组织来源的细胞因子、花生四烯酸的类二十烷酸产物以及雌激素和睾酮的代谢产物。与临床早期前列腺癌更快进展相关的生活方式因素越来越受到医疗保健提供者和公共卫生专业人员的关注。这项研究将在五年内完成，将确定肥胖与诊断时更具“侵袭性”前列腺癌相关的一些生物学原因，并降低男性通过手术治愈的机会。它还将揭示预防前列腺癌复发的方法，可能涉及新的或现有的药物或生活方式的改变。公共卫生相关性：与临床早期前列腺癌更快进展相关的生活方式因素越来越受到医疗保健提供者和公共卫生专业人员的关注。这项研究将在五年内完成，将确定肥胖与诊断时更具“侵袭性”前列腺癌相关的一些生物学原因，并降低男性通过手术治愈的机会。它还将揭示预防前列腺癌复发的方法，可能涉及新的或现有的药物或生活方式的改变。