Molecular Epidemiology of Prostate Cancer Outcomes: Genetics, Multilevel Environ

前列腺癌结果的分子流行病学：遗传学、多层次环境

• 批准号: 8820827
• 负责人: TIMOTHY R REBBECK
• 金额: $ 40.7万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8820827
• 关键词: Address; Adverse effects; African American; Age; American; Area; Biological Factors; Biological Markers; Biology; Cancer Etiology; Cessation of life; Characteristics; Complex; Data; Disease; Environmental Exposure; Environmental Risk Factor; European; Exposure to; Genetic; Genotype; Goals; Health Services Accessibility; Individual; Instruction; Length; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Medical Records; Molecular Epidemiology of Prostate Cancer; Neighborhoods; Nomograms; Outcome; Patients; Public Health; Questionnaires; Research; Risk; Risk Assessment; Risk Factors; Screening for cancer; Severities; Staging; Telomere Pathway; Time; Tissue Sample; cohort; contextual factors; deprivation; experience; follow-up; health disparity; improved; men; model building; mortality; outcome forecast; predictive modeling; prospective; response; screening; segregation; telomere; tumor

PROJECT SUMMARY (See instructions): Prostate cancer (PCa) is the most common non-cutaneous malignancy in US men and the second cause of cancer death, with age-adjusted mortality of 62.3 per 100,000 in African American (AA) and 25.6 per 100,000 in European American (EA) men. Although the high mortality from PCa represents a critical public health problem, our understanding of PCa etiology and predictors of poor outcomes remains limited. Screening can detect PCa at an early stage, but generalized use of screening of men at both high and low risk of unfavorable outcomes may result in unnecessary treatment for some and insufficient treatment in others. Thus, a critical public health goal is to optimize risk assessment and target cancer screening and treatment to reduce PCa mortality while minimizing over treatment and its negative side effects in men who are unlikely to experience unfavorable PCa outcomes. It is likely that the causes of unfavorable PCa outcomes are multifactorial and complex. Tumor and patient characteristics have been used to identify some men with poor prognosis. However, the potential additional contribution of biological or environmental factors to these predictive models is not well understood. The goals of the research proposed here are 1) to identify factors that predict PCa outcomes, and 2) to use this information to identify men who may benefit from specific screening and or treatment options. We hypothesize that long-term exposure to unfavorable individual-level and macro-environmental exposures influence PCa severity and access to health care. These exposures include area-level or neighborhood factors such as neighborhood deprivation and residential segregation. We further hypothesize that the response to these exposures is mediated by biomarkers. We propose to use a large, prospective cohort currently including 1,900 PCa cases with a projected average of 72 months of prospective follow at the time of analysis, tissue samples, geospatial data, questionnaire information, and medical records data to evaluate (1) the effect of tumor biomarkers on PCa aggressiveness and outcomes, (2) the effect of macroenvironmental contextual factors on biomarkers of unfavorable long-term exposures or PCa outcomes, and (3) Develop improved nomograms that include biomarkers, individual risk factors and macro-environmental factors (including factors identified in Project 1) to identify a multilevel set of predictors of PCa outcomes.

项目总结（见说明）： 前列腺癌（PCa）是美国男性中最常见的非皮肤恶性肿瘤，也是癌症死亡的第二大原因，非裔美国人（AA）的年龄校正死亡率为62.3/100，000，欧裔美国人（EA）为25.6/100，000。尽管前列腺癌的高死亡率是一个严重的公共卫生问题，但我们对前列腺癌病因学和预后不良的预测因素的了解仍然有限。 筛查可以在早期阶段检测PCa，但在不利结果的高风险和低风险男性中普遍使用筛查可能导致某些人不必要的治疗和其他人的治疗不足。因此，一个关键的公共卫生目标是优化风险评估和靶向癌症筛查和治疗，以降低PCa死亡率，同时最大限度地减少过度治疗及其对不太可能经历不利PCa结果的男性的负面副作用。 不利的PCa结局的原因可能是多因素和复杂的。肿瘤和患者特征已被用于识别一些预后不良的男性。然而，生物或环境因素对这些预测模型的潜在额外贡献还没有得到很好的理解。本研究的目标是：1）确定预测前列腺癌预后的因素，2）利用这些信息确定可能从特定筛查和/或治疗中获益的男性 选项.我们假设长期暴露于不利的个人水平和宏观环境暴露影响PCa的严重程度和获得医疗保健。这些风险包括地区或邻里因素，如邻里剥夺和居住隔离。我们进一步假设，对这些暴露的反应是由生物标志物介导的。我们建议使用一个大型的前瞻性队列，目前包括1，900例PCa病例，预计平均前瞻性随访时间为72个月， 分析时间、组织样本、地理空间数据、问卷信息和医疗记录数据，以评估（1）肿瘤生物标志物对PCa侵袭性和结果的影响，（2）宏观环境背景因素对不利的长期暴露或PCa结果的生物标志物的影响，和（3）开发包括生物标志物的改进列线图，个体风险因素和宏观环境因素（包括项目1中确定的因素），以确定PCa结果的多层次预测因素。