Genetic factors for race related prostate cancer.

 描述(由申请人提供)：主要的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的前列腺癌健康差距。一个主要的问题是，为什么与高加索人相比，非裔美国人男性的总体发病率更高，发病年龄更早，临床晚期疾病的比例更高，前列腺癌的骨转移和死亡率更高？这个项目的主要目标是调查前列腺癌健康差异的遗传基础，其基本原理是前列腺癌是美国非洲裔男性的主要癌症。尽管美国所有人口结构的前列腺癌筛查都更加积极，但人群之间的差异仍然存在。与高加索人相比，相当大比例的非裔美国人男性的总体发病率更高，发病年龄更早，临床晚期疾病的比例增加，前列腺癌的骨转移和死亡率增加。在诊断出男性前列腺癌后，存活率存在种族差异。因此，前列腺癌的发病率和死亡率对非裔美国男性来说是一个重大的公共卫生问题。最近的研究表明，在前列腺癌中，miRNAs发生了显著的变化。根据我们的初步数据，我们假设一组致癌miRNAs和抑癌基因miRNAs在非裔美国人中的差异表达谱可能针对一组前列腺癌特异基因，并可能导致非裔美国人前列腺癌的健康差异。抑癌基因miRNAs的作用机制是通过抑制癌基因和激活抑癌基因来实现的。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。所有目标都具有高度的针对性、集中性、创新性、临床意义、功能性和机械性。具体目标#1。研究miRNAs作为前列腺癌遗传基础的作用，与非裔美国人和高加索人的健康差异相比较。特定目的#2.研究致癌和抑癌基因miRNAs在种族相关前列腺癌中的功能意义和作用的分子机制。具体目标#3.研究miRNAs在非裔美国人和高加索人中差异表达的分子机制。影响：本申请具有很高的影响，因为它描述了一种与以前的尝试不同且更好的新概念和方法，因为一组miRNAs的差异表达可能解释了为什么非裔美国人比高加索人前列腺癌的发病率更高。该项目将确定新的miRNAs，这些miRNAs可以用作种族相关前列腺癌的遗传生物标志物和潜在的治疗靶点。

 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.