Genetic factors for race related prostate cancer.

 描述（由申请人提供）：主要问题或障碍是目前没有方法或途径来充分解决非裔美国人前列腺癌健康差异。一个主要的问题是，为什么非洲裔美国人与白人相比，前列腺癌的总体发病率更高，发病年龄更早，临床晚期疾病的比例增加，骨转移和死亡率增加？该项目的主要目标是调查前列腺癌健康差异的遗传基础，其理由是前列腺癌是美国非洲裔男性的主要癌症。尽管在美国所有人口统计学中对前列腺癌进行了更积极的筛查，但人群之间的差异仍然存在。与高加索人相比，相当比例的非洲裔美国男性具有较高的总体发病率、较早的发病年龄、临床晚期疾病的比例增加以及前列腺癌的骨转移和死亡率增加。男性前列腺癌诊断后的生存率存在种族差异。因此，前列腺癌的发病率和死亡率代表了非洲裔美国男性的一个重大公共卫生问题。最近的研究表明，miRNAs在前列腺癌中发生了显着改变。根据我们的初步数据，我们假设非裔美国人中一组致癌miRNA和肿瘤抑制miRNA的差异表达谱可能针对一组前列腺癌特异性基因，并可能导致非裔美国人的前列腺癌健康差异。肿瘤抑制miRNA的分子作用机制是通过抑制癌基因和激活肿瘤抑制基因。我们将通过分析在我们的特定目标下提出的一系列实验来检验这些假设。所有的目标都是高度集中的，集中的，创新的，临床意义，功能和机械的性质。具体目标#1。研究miRNAs作为非裔美国人与高加索人相比前列腺癌健康差异的遗传基础的作用。具体目标#2。研究种族相关前列腺癌中致癌和抑癌miRNAs的功能意义和分子作用机制。具体目标#3。研究非裔美国人和高加索人中miRNAs差异表达的分子机制。影响：本申请具有高影响力，因为它描述了一种新的概念和方法，其与先前的尝试不同且更好，因为一组miRNA的差异表达可以解释为什么非裔美国人与高加索人相比具有更高的前列腺癌发病率。该项目将鉴定可用作种族相关前列腺癌的遗传生物标志物和潜在治疗靶点的新型miRNA。

 DESCRIPTION (provided by applicant): The major problem or barrier is that there are currently no methods or approaches to adequately address prostate cancer health disparity in African Americans. A major question is why do African American men have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease and increased bone metastases and mortality from prostate cancer compared to Caucasians? The main goal of this project is to investigate the genetic basis of prostate cancer health disparities The rationale is that prostate cancer is the leading cancer among men of African descent in the USA. Despite more aggressive screening of prostate cancer across all demographics in the United States, disparities among populations persist. A substantial proportion of African American men have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease and increased bone metastases and mortality from prostate cancer compared to Caucasians. There are racial disparities in survival after diagnosis of prostate cancer in men. Therefore, prostate cancer incidence and mortality represent a significant public health problem in African American men. Recent studies have shown that miRNAs are significantly altered in prostate cancer. Based on our preliminary data, we hypothesize that the differential expression profile of a set of oncogenic miRNAs and tumor suppressor miRNAs in African Americans may target a set of prostate cancer specific genes and may contribute to the prostate cancer health disparity in African Americans. The molecular mechanisms of action of tumor suppressor miRNAs are through repressing oncogenes and activating tumor suppressor genes. We will test these hypotheses through analyses of a series of experiments proposed under our specific aims. All the aims are highly focused, centralized, innovative, clinically significant, functional and mechanistic in nature. Specific Aim # 1. Investigate the role of miRNAs as the genetic basis of prostate cancer health disparity in African Americans as compared to Caucasians. Specific Aim # 2. Investigate the functional significance and molecular mechanisms of action of oncogenic and tumor suppressor miRNAs in race-related prostate cancer. Specific Aim # 3. Investigate the molecular mechanisms of differential expression of miRNAs in African Americans and Caucasians. Impact: The present application has high impact because it describes a novel concept and approach that is different and better from the previous attempts since differential expression of a set of miRNAs may explain why African Americans have higher incidence of prostate cancer compared to Caucasians. This project will identify novel miRNAs that can be used as genetic biomarkers and potential therapeutic targets for race-related prostate cancer.