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

描述（由申请人提供）：尽管白人美国人（CA）的乳腺癌总体发病率较高，但非裔美国人（AA）中50岁以下女性的乳腺癌发病率较高。此外，AA女性在诊断时往往患有更晚期的乳腺癌。导致早发性侵袭性乳腺癌发病率增加的潜在因素知之甚少。假设：我们的假设是，在非洲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畸变模式相关。目的：为了更好地理解乳腺癌中观察到的种族差异的遗传基础，将分析来自亚拉巴马AA和CA患者的乳腺肿瘤的染色体改变和组织病理学特征。从长远来看，我们寻求确定在早发性乳腺癌的发展和进展中发挥核心作用的基因组位点。具体目标：具体目标是1。使用比较基因组杂交（CGH）比较亚拉巴马早发性乳腺癌患者（年龄<50岁）的染色体畸变谱，2.描述亚拉巴马AA和CA患者中早发性乳腺癌的组织病理学特征。研究设计：将采用阵列CGH检查每份样本中的染色体畸变，并评估组间拷贝数频率的显著差异。将收集每个种族组的病理学信息并进行评价。已知预后指标（例如，p53、p27、ER、PR和HER-2/neu）和通过阵列-CGH显示的候选基因座。相关性：这项研究有可能发现导致早发性乳腺癌的新基因，并可能发现新的预后和治疗靶点。此外，与特定的组织病理学因素相关的染色体畸变模式的鉴定可能会导致未来应用CGH技术评估乳腺癌预后。声明：与CA相比，AA的早发性乳腺癌发病率增加，死亡率更高。影响这些健康差异的遗传因素定义不清。

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.