A high resolution comparative analysis of early onset breast cancer by race

按种族划分的早发乳腺癌的高分辨率比较分析

• 批准号: 7320731
• 负责人: TYESHA L FARMER
• 金额: $ 2.89万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-27 至 2009-09-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7320731
• 关键词: African American; Age; Age of Onset; Alabama; BRCA1 gene; BRCA2 gene; Biological Factors; Breast; Cancer Etiology; Cancer Patient; Cancer Prognosis; Cancer-Predisposing Gene; Candidate Disease Gene; Caucasians; Caucasoid Race; Cessation of life; Chromosome abnormality; Clinical; Computer software; Coupled; Cyclin E; Data; Development; Diagnosis; Diagnostic Neoplasm Staging; Disease; Ethnic group; Evaluation; Exhibits; Frequencies; Future; Genes; Genetic; Genome; Genomics; Hereditary Breast Carcinoma; Histopathology; Hormone Receptor; Immunohistochemistry; Incidence; Inherited; Investigation; Lead; Logistic Regressions; Malignant neoplasm of ovary; Mammary Neoplasms; Modeling; Molecular; Molecular Profiling; Mutation; Normal tissue morphology; Numbers; Oncogenic; Pathway interactions; Patients; Pattern; Phase; Phenotype; Play; Population; Process; Property; Race; Rate; Relative Risks; Reporting; Resolution; Role; Sampling; Screening procedure; Staging; Survival Rate; TP53 gene; Techniques; Time; Tumor Biology; Tumor stage; Variant; Woman; base; cancer health disparity; caucasian American; comparative; comparative genomic hybridization; design; early onset; experience; health disparity; malignant breast neoplasm; mortality; novel; novel therapeutics; outcome forecast; p27 Cell Cycle Protein; p27 Enzyme Inhibitor; prognostic; protein expression; reproductive; size; therapeutic target; trend; tumor

DESCRIPTION (provided by applicant): Although the overall incidence of breast cancer is higher in Caucasian Americans (CA), the incidence of breast cancer in women below the age of 50yrs is higher in African-Americans (AA). In addition, AA women tend to present with more advanced stage breast cancer at the time of diagnosis. The underlying factors contributing to this increased incidence of early onset aggressive breast cancer are poorly understood. HYPOTHESIS: Our hypothesis is that the differences in tumor phenotype observed between African-American and Caucasian early onset breast cancer patients correlate with specific patterns of genomic aberrations. OBJECTIVE: To better understand the genetic basis for the observed racial disparities in breast cancer, chromosomal alteration and histopathologic profiles of breast tumors from Alabama AA and CA patients will be analyzed. In the long term, we seek to identify genomic loci that play a central role in the development and progression of early onset breast cancer. SPECIFIC AIMS: The specific aims are 1. Compare chromosomal aberration profiles in Alabama early onset breast cancer patients (Age <50yrs) using comparative genomic hybridization (CGH), 2. Characterize the histopathology of early onset breast cancer in Alabama AA and CA patients. STUDY DESIGN: Array CGH will be employed to examine chromosomal aberrations in each sample, and significant differences in copy number frequency between groups will be assessed. Pathological information will be gathered and evaluated for each ethnic group. Expression levels of known prognostic indicators (e.g., p53, p27, ER, PR and HER-2/neu) and candidate loci as revealed by array-CGH will be determined. RELEVANCE: The proposed investigation has the potential to identify novel genes that contribute to early onset breast cancer and possibly identify new prognostic and therapeutic targets. In addition, identification of patterns of chromosomal aberration associated with specific histopathologic factors may lead to future application of the CGH technique in assessment of breast cancer prognosis. LAY STATEMENT: Compared to CA, AA have an increased incidence of early onset breast cancer with higher mortality rates. Genetic factors influencing these health disparities are poorly defined.

描述(申请人提供)：尽管乳腺癌的总体发病率在高加索美国人(CA)中较高，但50岁以下女性的乳腺癌发病率在非裔美国人(AA)中较高。此外，再生障碍性贫血妇女在确诊时往往会出现更晚期的乳腺癌。导致早发性侵袭性乳腺癌发病率增加的潜在因素尚不清楚。假设：我们的假设是，在非裔美国人和高加索人早发性乳腺癌患者之间观察到的肿瘤表型差异与特定的基因组异常模式相关。目的：分析阿拉巴马州AA和CA患者乳腺肿瘤的染色体改变和组织病理学特征，以更好地了解乳腺癌存在种族差异的遗传基础。从长远来看，我们寻求确定在早发性乳腺癌的发生和发展中发挥核心作用的基因组基因座。具体目标：1.用比较基因组杂交(CGH)方法比较阿拉巴马州50岁早发性乳腺癌患者的染色体畸变率；2.描述阿拉巴马州AA和CA患者早发性乳腺癌的组织病理学特征。研究设计：将使用阵列CGH检查每个样本中的染色体畸变率，并评估不同组之间拷贝数频率的显著差异。将收集和评估每个民族的病理信息。将确定已知预后指标(例如，p53、p27、ER、PR和HER-2/neu)和ARRAY-CGH揭示的候选基因的表达水平。相关性：这项拟议的研究有可能确定与早发性乳腺癌有关的新基因，并可能确定新的预后和治疗靶点。此外，识别与特定组织病理因素相关的染色体异常模式可能导致未来CGH技术在乳腺癌预后评估中的应用。LAY声明：与CA相比，AA的早发性乳腺癌发病率更高，死亡率更高。影响这些健康差异的遗传因素还没有明确的定义。