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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

基本信息

批准号：
7919389
负责人：
E. Shyam P REDDY
金额：
$ 1.45万
依托单位：
MOREHOUSE SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
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/7919389
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 Receptor Gene Registries Regulation Research Research Personnel Resistance Risk Risk Factors Schools Specific qualifier value Stratification TNF gene TNFSF6 gene Techniques Testing Therapeutic Intervention 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 development case control cytokine experience functional genomics high risk interest medical schools meetings men multidisciplinary neoplastic cell programs racial difference receptor sex sound tool

项目摘要

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.

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