Genetic factors for race related prostate cancer.

种族相关前列腺癌的遗传因素。

基本信息

批准号：
8874808
负责人：
RAJVIR DAHIYA
金额：
$ 31.81万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8874808
关键词：
3&apos Untranslated Regions 5&apos Untranslated Regions Address African African American Age of Onset Apoptosis Benign Binding Biological Assay Caucasians Cell Cycle Cell Line CpG Islands DNA Methylation DNA Modification Methylases DNA Sequence DNA copy number DNMT3B gene DNMT3a Data Diagnosis Gene Targeting Genes Genetic Genetic Markers Goals Histone Acetylation Human In Situ Hybridization In Vitro Incidence Luciferases Malignant Neoplasms Malignant neoplasm of prostate Mediating Messenger RNA Metastatic Neoplasm to the Bone Methods Methylation MicroRNAs Molecular Molecular Mechanisms of Action Molecular Profiling Monitor Nature Oncogenes Oncogenic Population Promoter Regions Prostate Public Health Race Repression Role Sampling Screening for Prostate Cancer Series Staging Structure of base of prostate Techniques Testing Time Tissues Tumor Suppressor Genes Tumor Suppressor Proteins United States advanced disease base cancer health disparity cell growth clinically significant demographics differential expression histone modification innovation men mortality novel public health relevance racial disparity research study sodium bisulfite therapeutic target

项目摘要

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.

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可以充分解决非裔美国人的前列腺癌健康差异。一个主要问题是为什么非裔美国男性的总体发病率更高、年龄更早。与白种人相比，前列腺癌的发病率、临床晚期疾病比例增加以及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。其基本原理是，前列腺癌是男性中最主要的癌症。的尽管美国对所有人群的前列腺癌筛查都更加积极，但很大一部分非裔美国男性的总体发病率较高，发病年龄较早，临床晚期疾病的比例也较高。与白种人相比，前列腺癌的骨转移和死亡率增加。男性诊断出前列腺癌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是非裔美国男性的一个重大公共卫生问题。 miRNA 显着存在于根据我们的初步数据，我们发现非裔美国人中一组致癌 miRNA 和抑癌 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前列腺癌健康差异。抑癌 miRNA 的作用是通过抑制癌基因和激活抑癌基因来实现的，我们将通过对我们特定目标下提出的一系列实验进行分析来检验这些假设。具有创新性、临床意义、功能性和机制性。具体目标#1。与白种人相比，研究 miRNA 作为非裔美国人前列腺癌健康差异遗传基础的作用。具体目标#2。研究功能意义和分子机制。致癌和肿瘤抑制 miRNA 在种族相关前列腺癌中的作用。具体目标#3。研究非裔美国人和白种人中 miRNA 差异表达的分子机制。本申请具有很高的影响力，因为它描述了一种与之前的尝试不同且更好的新概念和方法，因为一组 miRNA 的差异表达可以解释为什么非裔美国人与白种人相比具有更高的前列腺癌发病率。该项目将确定新的概念和方法。 miRNA 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。