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.

项目摘要（请参阅说明）： 前列腺癌（PCA）是美国男性中最常见的非乳头恶性肿瘤，也是癌症死亡的第二个原因，在非洲裔美国人（AA）中，年龄调整后的死亡率为每100,000人62.3，在欧美（EA）男性中，每10万人（AA）和每100,000名。尽管PCA的高死亡率代表了一个关键的公共卫生问题，但我们对PCA病因的理解和对不良结果的预测因素仍然有限。 筛查可以在早期阶段检测到PCA，但是在不利结果的高风险和低风险中对男性进行全面使用可能会导致一些不必要的治疗方法，而另一些人的治疗则不足。因此，一个关键的公共卫生目标是优化风险评估并靶向癌症筛查和治疗，以降低PCA死亡率，同时最大程度地减少治疗及其对不太可能经历不利PCA结果的男性的负面影响。 不利的PCA结果的原因可能是多因素和复杂的。肿瘤和患者特征已被用来识别一些预后不良的男性。但是，生物学或环境因素对这些预测模型的潜在额外贡献尚不清楚。这里提出的研究的目标是1）确定预测PCA结果的因素，以及2）使用此信息来识别可能受益于特定筛查和或治疗的男人 选项。我们假设长期暴露于不利的个人级别和宏观环境暴露会影响PCA的严重程度并获得医疗保健。这些暴露包括面积级别或邻里因素，例如邻里剥夺和住宅隔离。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。我们建议使用目前的大型，预期的队列，包括1,900例PCA案件，预计平均有72个月的前瞻性跟随 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的侵略性和结果的影响，（2）宏观环境上下文因素对生物标志物对不利长期暴露或PCA的不利影响的生物标志物的影响，包括基于生物的样子，以及（3）型号，包括（3）均应（3），以及（3），以及（3），以及（3），包括（3）因素（包括项目1中确定的因素）以确定一组PCA结果的多级预测指标。