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

高危非洲裔美国人中多发性骨髓瘤的遗传易感性

• 批准号: 7726956
• 负责人: E. Shyam P REDDY
• 金额: $ 1.83万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7726956
• 关键词: 1q21; Accounting; Address; Admixture; Advisory Committees; Affect; Affinity; African American; Alabama; Alleles; American; Apoptosis; B lymphoid malignancy; B-Cell Activation; B-Lymphocytes; Binding; Bone Marrow; California; Cancer Center; Candidate Disease Gene; Cell Death Process; Chairperson; Chromosome abnormality; Chromosomes; Clinical Management; Comprehensive Cancer Center; Connecticut; Coupled; DNA Resequencing; Data; Development; Dose; Ensure; Epidemiologist; Etiology; European; Evaluation; Extramural N.I.H. Research Support; FCGR2A gene; FCGR2B gene; FCGR2C gene; FCGR3A gene; FCGR3B gene; Family Study; Fc Receptor; Feasibility Studies; First Degree Relative; Fred Hutchinson Cancer Research Center; Frequencies; Funding; Gene Activation; Gene Cluster; Gene Family; Genes; Genetic; Genetic Predisposition to Disease; Genomics; Genotype; Goals; Haplotypes; Hereditary Disease; Homeostasis; Hospitals; Immunity; Immunogenetics; Immunoglobulin G; Immunoglobulins; Incidence; Inflammatory; Interleukin-10; Investigation; Joints; Laboratories; Lesion; Link; Linkage Disequilibrium; Logistic Regressions; Los Angeles; Lytic; Mediating; Minority; Modeling; Molecular; Molecular Epidemiology; Monozygotic Twinning; Monozygotic twins; Multiple Myeloma; Myeloid Cells; Oregon; Pathogenesis; Pathway interactions; Patients; Phase; Phenotype; Plasma Cells; Population; Population Study; Predisposition; Race; Rate; Receptor Gene; Registries; Regulation; Research; Research Personnel; Resistance; Risk; Risk Factors; Specific qualifier value; Stratification; TNF gene; TNFSF6 gene; Techniques; Testing; Therapeutic Intervention; Thinking; Time; Training; Tumor Necrosis Factor Receptor; Universities; University Hospitals; Variant; Washington; Woman; Work; base; bis(3-bis(4-chlorophenyl)methyl-4-dimethylaminophenyl)amine; bone; cancer health disparity; career; case control; cytokine; experience; functional genomics; interest; medical schools; men; multidisciplinary; neoplastic cell; programs; racial difference; receptor; sex; sound; tool

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.

该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）通过高风险非裔美国人中选定候选基因的独立和联合效应 （AA）人口。该假设是影响免疫球蛋白结合的基因的常见变异为 B 细胞激活和稳态与 MM 的存在相关。为了解决这个假设，我们 打算测试 (1) FCGR2A 和候选基因着丝粒和端粒是否符合该假设 易感位点（染色体 1q21-24）通过连锁与高风险 AA 人群中的 MM 相关 不平衡（LD）来定义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细胞凋亡的抵抗，与 高危 AA 人群对 MM 的易感性。使用来自大学的案例和对照 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 加利福尼亚州 (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。汇总的研究人群将代表 迄今为止 AA 患者中 MM 群体最多，这将有助于对 MM 进行全面评估 MM 易感性因种族而异。这些方法共同提供了快速实现的最佳机会 利用异常 B 细胞激活和稳态与 MM 的目标关系并生成 研究功能基因组学作为针对高风险人群的工具所需的初步数据 谁可能受益于个体化临床管理或治疗干预。候选人是新人 没有当前或过去的 NIH 校外研究支持的独立研究者将应用他们的 表现出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 在这个神秘的过程中，参与对 B 细胞激活和体内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大部分工作将在 UAB 进行，但应该指出的是，Dr. 伊丽莎白·布朗（Elizabeth Brown）是一位新的无资金资助的调查员，她对癌症健康差异表现出兴趣， 曾担任俄勒冈癌症中心妇女和少数族裔工作组的联合主席。 该项目显然符合 U54 的目标之一，即加强 UAB 的癌症差异研究。 一位年轻分子流行病学家在 UAB 研究癌症差异方面的职业发展 对于我们最终理解造成差异的任何分子原因以及 阿拉巴马大学癌症差异分子流行病学项目的开发。 MSM 的 Reddy 博士将 作为该项目的联合领导者将提供他在表征基因组方面的丰富专业知识 易位是该项目的重要组成部分。 Brown 的湿实验室经验有限， 让雷迪博士的实验室可用于多种相关实验室台架技术的培训对于雷迪博士来说至关重要。 布朗的训练。