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: 8624548
• 负责人: TIMOTHY R REBBECK
• 金额: $ 17.15万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8624548
• 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; Modeling; 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; 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.

项目摘要（参见说明）： 前列腺癌 (PCa) 是美国男性最常见的非皮肤恶性肿瘤，也是癌症死亡的第二大原因，非洲裔美国人 (AA) 男性中年龄调整死亡率为每 100,000 人 62.3 人，欧洲裔美国人 (EA) 男性为每 100,000 人 25.6 人。尽管 PCa 的高死亡率是一个严重的公共卫生问题，但我们对 PCa 病因和不良结果预测因素的了解仍然有限。 筛查可以在早期发现前列腺癌，但对不良结果高风险和低风险的男性进行普遍筛查可能会导致某些人接受不必要的治疗，而另一些人则得不到充分的治疗。因此，一个关键的公共卫生目标是优化风险评估和有针对性的癌症筛查和治疗，以降低前列腺癌死亡率，同时最大限度地减少过度治疗及其对不太可能经历不利前列腺癌结果的男性的负面影响。 PCa 不良结果的原因可能是多因素且复杂的。肿瘤和患者特征已被用来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尚不清楚。本文提出的研究目标是 1) 确定预测 PCa 结果的因素，2) 使用此信息来确定可能受益于特定筛查和/或治疗的男性 选项。我们假设长期暴露于不利的个人水平和宏观环境会影响前列腺癌的严重程度和获得医疗保健的机会。这些风险包括区域层面或邻里因素，例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。我们建议使用目前包括 1,900 例 PCa 病例的大型前瞻性队列，预计平均随访时间为 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长期暴露或 PCa 结果的生物标志物的影响，以及 (3) 开发改进的列线图，包括生物标志物、个体风险因素和宏观环境 因素（包括项目 1 中确定的因素）来确定 PCa 结果的多级预测因素。