Genetic Susceptibility of Multiple Myeloma in a High-Risk African American Popula

这项试点和可行性研究的目的是了解多发性骨髓瘤的遗传易感性 (MM)通过选择候选基因在高风险非洲裔美国人中的独立和联合作用， (AA)人口假设是影响免疫球蛋白结合的基因中的常见变异， 以及B细胞活化和稳态与MM的存在相关。为了解决这一假设，我们 目的是测试（1）FCGR 2A和候选基因是否与这个假定的着丝粒和端粒相关， 遗传易感基因座（染色体1 q21 -24）与高危AA人群中的MM相关 不平衡（LD），以确定种族特异性单倍型块和（2）候选基因中的常见变异， TNF和TNFR超家族参与浆细胞对凋亡的抗性，与 高危AA人群中MM的易感性。使用来自美国大学的病例和对照， 亚拉巴马大学伯明翰分校（UAB），莫尔豪斯医学院-格雷迪医院，南方大学 加州（USC）、华盛顿大学（UW）、韦恩州立大学和SEER注册中心，我们打算 利用MM易感性的靶向基因组学关系。汇总研究人群将代表 到目前为止，AA患者中MM的最大人群，这将允许全面评价 MM易感性在人种中呈二态性。这些方法共同提供了最佳机会， 利用异常B细胞活化和稳态与MM的靶向关系， 研究功能基因组学作为针对高危人群的工具所需的初步数据 这些患者可能受益于个体化临床管理或治疗干预。候选人是一个新的 没有当前或过去的校外NIH研究支持的独立研究者， 在分子流行病学和免疫遗传学方面的专业知识， 参与B细胞活化和稳态的基因活化的途径， 炎症介导的B细胞恶性肿瘤。 尽管与该项目相关的大部分工作将在UAB进行，但应该指出的是， 伊丽莎白·布朗是一位新的无资金支持的研究人员，她对癌症健康差异表现出了浓厚的兴趣， 她曾担任俄勒冈州癌症中心妇女和少数民族工作组的联合主席。 该项目显然符合U 54的目标之一，以加强UAB的癌症差异研究。 一位年轻的分子流行病学家在UAB研究癌症差异方面的职业发展是 这对我们最终理解差异的任何分子原因以及 在UAB开发癌症差异分子流行病学计划。Dr. Reddy at MSM who will 作为该项目的共同领导人，他将在基因组特征方面提供相当多的专业知识， 作为这个项目的一个重要组成部分。布朗的湿实验室经验有限， 让雷迪博士的实验室提供多种相关实验室工作台技术的培训对雷迪博士来说至关重要。 布朗的训练

The goal of this pilot and feasibility study is to understand the genetic susceptibility to Multiple Myeloma (MM) through the independent and joint effects of select candidate genes in a high-risk African American (AA) population. The hypothesis is that common variation in genes that influence immunoglobulin binding as well as B cell activation and homeostasis correlate with presence of MM. To address this hypothesis, we intend to test whether (1) FCGR2A and candidate genes centromeric and telomeric to this putative susceptibly locus (chromosome 1q21-24) are associated with MM in a high-risk AA population using linkage disequilibrium (LD) to define race-specific haplotype blocks and (2) common variation in candidate genes in the TNF and TNFR superfamily, involved in plasma cell resistance to apoptosis, are associated with susceptibility to MM in a high-risk AA population. Using cases and controls pooled from the University of Alabama at Birmingham (UAB), the Morehouse School of Medicine-Grady Hospital, University of Southern California (USC), University of Washington (UW), Wayne State University and the SEER registry, we intend to exploit targeted genomics relationships of MM susceptibility. The pooled study population will represent the largest population to date of MM among AA patients, which will allow for a comprehensive evaluation of MM susceptibility that is dimorphic by race. Together these approaches offer the best opportunity to rapidly exploit targeted relationships of aberrant B cell activation and homeostasis with MM and to generate preliminary data necessary to investigate functional genomics as a tool for targeting high-risk populations who may benefit from individualized clinical management or therapeutic intervention. The candidate is a new independent investigator without current or past extramural NIH research support who will apply their demonstrated expertise in molecular epidemiology and immunogenetics to the understanding of common pathways involved in the activation of genes important for B cell activation and homeostasis in this enigmatic inflammatory-mediated B cell malignancy. Although much of the work associated with this project will be conducted at UAB, it should be noted that Dr. Elizabeth Brown is a new unfunded investigator with a demonstrated interest in cancer health disparities, having served as co-chairperson for the Women and Minorities Task Force of the Oregon Cancer Center. This project clearly meets one of the goals of the U54, to enhance the cancer disparity research at UAB. The development of the career of a young molecular epidemiologist in cancer disparity at UAB research is critically important to our ultimate understanding of any molecular causes for disparity and to the development of a cancer disparity molecular epidemiology program at UAB. Dr. Reddy at MSM who will serve as a Co-Leader for the project will provide his considerable expertise in characterizing genomic translocations as an important component of this project. Brown's wet laboratory experience is limited and having Dr. Reddy's lab available for training in multiple pertinent laboratory bench techniques is critical to Dr. Brown's training.