Basic Cancer Research in Cancer Health Disparities

癌症健康差异的基础癌症研究

基本信息

批准号：
8725605
负责人：
RADOSLAV GOLDMAN
金额：
$ 28.2万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-19 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8725605
关键词：
Affect African American Alleles Androgens Androstenes Basic Cancer Research Biological Assay Biological Availability Biological Factors Blood Circulation C-terminal Cancer Etiology Case Series Case-Control Studies Cells Collaborations Data Databases Detection Development Disease Drug or chemical Tissue Distribution Endocrine Environment Equilibrium Estradiol Estrogens Freezing Genetic Polymorphism Genomics Genotype GlobulinN Glycols Glycoproteins Goals Gonadal Steroid Hormones Human Immunohistochemistry Intervention Laboratories Laminin Malignant neoplasm of prostate Measurement Measures Methodology Methods N-Glycosylation Site Nucleotides Paraffin Embedding Pathway interactions Plasma Population Predisposition Prostate Protein C Protein Glycosylation Proteins Proteome Reagent Research Research Infrastructure Resource Informatics Resources Sampling Serum Sex Hormone-Binding Globulin Signal Transduction Site Stanolone Steroids Testosterone Time Tissues Variant base cancer health disparity cancer prevention cancer risk case control caucasian American comparative glycosylation health disparity high risk improved male men novel prostate cancer prevention prostate carcinogenesis protein distribution steroid hormone tissue resource tumor tumor progression web-accessible

项目摘要

DESCRIPTION (provided by applicant): Prostate cancer is the most common lethal tumor among US males yet little is known about its causative mechanisms. This study proposes to examine how glycosylation of sex hormone binding globulin (SHBG) affects steroid hormone signaling in prostate cancer. We will define the impact of SHBG glycosylation, including the D327N SHBG polymorphism, on steroid hormone associated prostate cancer risk and disparity in African and Caucasian Americans. Protein glycosylation is critical for interaction of prostate cells with its environment. We will evaluate how glycosylation of SHBG affect the distribution of the protein between plasma and tissue and how this affects disease development. The quantification of the SHBG glycoforms will be achieved by novel LC-MS assays. In addition, we will comprehensively summarize the impact of polymorphisms on N-glycosylation in the human proteome. Our hypothesis is that prostate cancer risk and progression are related to the variability in the glycosylation of SHBG. Our objective is to perform quantitative mass spectrometric assays of SHBG glycosylation in conjunction with measurement of steroid hormones. We will select men for phenotypic characterization by genotyping of a case control population with 50% African American representation. In addition, we will genotype a case series for which both serum and tissue are available. Steroid hormones will be measured by GC-MS. We will analyze the SHBG glycoforms and steroid hormones at the tissue level and in the circulation. The study is expected to fill important gaps in our understanding of prostate cancer etiology and progression. The analysis of SHBG glycoforms will provide new information on the biological factors underlying prostate carcinogenesis. The results are expected to improve prostate cancer prevention, detection and intervention strategies.

描述（由申请人提供）：前列腺癌是美国男性中最常见的致死性肿瘤，但对其病因机制知之甚少。这项研究建议研究性激素结合球蛋白（SHBG）的糖基化如何影响前列腺癌中类固醇激素信号传导。我们将定义SHBG糖基化的影响，包括D327N SHBG多态性，对非洲和高加索美国人的类固醇激素相关的前列腺癌风险和差异。蛋白质糖基化对于前列腺细胞与其环境的相互作用至关重要。我们将评估SHBG的糖基化如何影响血浆和组织之间蛋白质的分布，以及这如何影响疾病发育。新型LC-MS分析将实现SHBG糖型的定量。此外，我们将全面总结多态性对人蛋白质组N-糖基化的影响。我们的假设是，前列腺癌的风险和进展与SHBG糖基化的变异性有关。我们的目标是在测量类固醇激素的结合下对SHBG糖基化进行定量质谱测定。我们将通过对非裔美国人代表50％的病例控制人群进行基因分型来选择男性进行表型表征。此外，我们将基因型一个病例系列，可为血清和组织提供。类固醇激素将通过GC-MS测量。我们将在组织水平和循环中分析SHBG糖型和类固醇激素。预计该研究将填补我们对前列腺癌病因和进展的理解中的重要空白。 SHBG糖型的分析将提供有关前列腺致癌作用生物学因素的新信息。结果预计将改善前列腺癌的预防，检测和干预策略。