Molecular Epidemiology of Prostate Cancer Outcomes: Genetics, Multilevel Environ

项目总结(见说明)： 前列腺癌(PCA)是美国男性最常见的非皮肤恶性肿瘤，是癌症死亡的第二大原因，非裔美国人(AA)的年龄调整死亡率为62.3/10万，欧洲裔美国人(EA)男性的年龄调整死亡率为25.6/10万。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的病因和不良结果的预测因素的了解仍然有限。 筛查可以在早期阶段发现前列腺癌，但普遍使用对结局不利的高风险和低风险男性进行筛查可能会导致一些人不必要的治疗，而另一些人的治疗不足。因此，一个关键的公共卫生目标是优化风险评估并针对癌症筛查和治疗，以降低PCA死亡率，同时将过度治疗及其对那些不太可能经历不良PCA结果的男性的负面副作用降至最低。 PCa预后不良的原因可能是多因素的和复杂的。肿瘤和患者的特征已经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还没有被很好地理解。这项研究的目标是1)确定预测PCa结果的因素，2)使用这些信息来确定哪些男性可能从特定的筛查和/或治疗中受益 选择。我们假设长期暴露在不利的个人水平和宏观环境中会影响前列腺癌的严重程度和获得医疗保健的机会。这些风险暴露包括地区级或邻里因素，如社区剥夺和居住隔离。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1900例PCa病例，预计平均72个月的预期随访时间为 分析时间、组织样本、地理空间数据、问卷信息和病历数据，以评估(1)肿瘤生物标记物对PCA侵袭性和结果的影响，(2)大环境背景因素对不良长期暴露或PCA结果的生物标记物的影响，以及(3)开发包括生物标记物、个体风险因素和宏观环境因素(包括项目1中确定的因素)的改进的诺模图，以确定一组多水平的PCA结果预测因素。

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.