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

这项试点和可行性研究的目标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危非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的共同变异 以及B细胞的激活和动态平衡与MM的存在相关。为了解决这一假说，我们 打算测试(1)FCGR2A和候选基因着丝粒和端粒是否与这一推定有关 易感基因(染色体1q21-24)与多发性骨髓瘤相关的高危再生障碍性贫血人群使用连锁 不平衡(LD)来确定小种特有的单倍型区块和(2)候选基因的共同变异 参与浆细胞抗凋亡的肿瘤坏死因子和肿瘤坏死因子受体超家族与 再生障碍性贫血高危人群对多发性骨髓瘤的易感性。使用来自伊利诺伊大学的案例和对照 阿拉巴马州伯明翰分校(UAB)南方大学莫尔豪斯医学院-格雷迪医院 加州大学(南加州大学)、华盛顿大学(UW)、韦恩州立大学和SEER注册，我们打算 目的：探索MM易感性的靶向基因组学关系。汇集的研究人群将代表 迄今为止AA患者中最大的MM人群，这将允许对 MM易感性因种族而异。这些方法结合在一起，提供了快速 利用异常B细胞激活和动态平衡与MM的靶向关系并生成 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 谁可能受益于个体化的临床管理或治疗干预。这位候选人是一位新来的 没有现任或过去NIH外部研究支持的独立调查员将应用他们的 展示了分子流行病学和免疫遗传学方面的专业知识，以了解常见的 在这个谜中，涉及对B细胞激活和动态平衡至关重要的基因激活的途径 炎症介导的B细胞恶性肿瘤。 尽管与该项目相关的许多工作都将在UAB进行，但应该指出的是，Dr。 伊丽莎白·布朗是一名新的无资金支持的研究员，她对癌症健康差异表现出了兴趣， 曾担任俄勒冈州癌症中心妇女和少数族裔工作组的联合主席。 这个项目显然符合U54的目标之一，即加强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 对于我们最终理解造成差异的任何分子原因以及 亚利桑那大学癌症差异分子流行病学项目的发展。MSM的雷迪博士将 作为该项目的联合负责人，将为他提供大量的基因组特征方面的专业知识 将易位作为该项目的一个重要组成部分。布朗的湿实验室经验是有限的 让雷迪博士的实验室可以进行多种相关实验室工作台技术的培训，这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.