Biological Variants Underlying Racial Differences in Lymphoma

淋巴瘤种族差异背后的生物变异

基本信息

批准号：
8389463
负责人：
CHRISTOPHER R FLOWERS
金额：
$ 18.02万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-23 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8389463
关键词：
Address Affect Age Alabama Algorithms Antibody Therapy Area B-Lymphocytes Biological Clinical Clinical Data Clinical Pathology Cohort Studies Collection Combination Drug Therapy Cox Models Data Data Set Diagnosis Disease Employment Frequencies Gene Expression Profiling Gene Mutation Genes Genetic Hematologic Neoplasms Immunohistochemistry Immunotherapy Incidence Inferior Insurance Insurance Coverage International Prognostic Index Left Life Logistic Regressions Lymphoma Malignant - descriptor Malignant Neoplasms Medicaid MicroRNAs Molecular Profiling Multivariate Analysis Mutate Mutation Non-Hodgkin&apos s Lymphoma Normal tissue morphology Oncogenes Outcome Patients Pattern Pharmacy facility Prevalence Prognostic Factor Protein Isoforms RNA Splicing Race Records Research Research Personnel Risk Sample Size Sampling Sequence Analysis Staging Structure of germinal center of lymph node Subgroup Tissue Microarray Tissues Treatment Protocols Uninsured United States Universities Variant Work base cancer health disparity chemotherapy clinically significant cohort comparative exome gene discovery hazard high risk large cell Diffuse non-Hodgkin&apos s lymphoma low socioeconomic status novel population based racial difference response treatment response tumor

项目摘要

DESCRIPTION (provided by applicant): Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in the US, affecting ~22,000 people/year. If untreated 92% of DLBCL die within 1 year, however, with modern combinations of chemotherapy and immunotherapy >50% of patients are cured, making DLBCL a clinically significant disease for examining cancer disparities. We discovered that black patients with DLBCL in the United States, are diagnosed at an age a decade younger age than whites (average age 53 vs. 70 years), are more likely to have advance stage disease, be uninsured or Medicaid insured, reside in the lowest socioeconomic status areas, and are less likely to have received modern chemotherapy. We confirmed these differences in age and stage in a second US population-based data set, and found blacks also had worse 5-year survival (38% vs. 46%). However, in separate studies at Emory and University of Alabama-Birmingham (UAB) and our combined study, we found again that black patients presented at a significantly younger age and still had worse survival even when the exact same treatment was given. Two biologically different subtypes of DLBCL can be identified that have different survival, Germinal center B-cell (GCB) DLBCL: 60% 5-year survival and activated B-cell (ABC) DLBCL: 35%. We propose to examine relationships between these biological variants and racial differences in DLBCL. Based on a widespread analysis of genes in DLBCL tumors and matched normal tissue, we helped identified 15 genes that are differentially mutated in ABC and GCB DLBCL and seek to determine if these differ by race. The main aims are: 1) To examine racial differences in the prevalence of ABC-like DLBCL and explore the relationships between ABC subtype, race and survival, and 2) To examine racial differences in novel genes differentially mutated in ABC-like DLBCL. We identified 433 DLBCL patients from the Emory and UAB cohort studies with available tissue blocks and clinical data. We are collecting demographic, insurance, employment, treatment, response and survival data, will construct a tissue microarray, and will perform IHC subtyping, mutation and expression profiling. PUBLIC HEALTH RELEVANCE: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in the US, affecting ~22,000 people/year. If left untreated nearly all patients live less than one year, however, with modern combinations of chemotherapy and antibody therapy more than 50% of patients are cured of their lymphoma, making DLBCL an ideal disease for studying cancer disparities. We discovered that black patients with DLBCL are diagnosed at a younger age than whites, more likely to have advanced stage disease, and have worse survival even when the same treatment is given, and want to determine whether a poor risk biological subtype of DLBCL is more common in black patients.

描述（由申请人提供）：弥漫性大 B 细胞淋巴瘤 (DLBCL) 是美国最常见的淋巴瘤，每年影响约 22,000 人。然而，如果未经治疗，92% 的 DLBCL 会在 1 年内死亡，而通过现代化疗和免疫疗法的结合，超过 50% 的患者可以治愈，这使得 DLBCL 成为检查癌症差异的临床重要疾病。我们发现，在美国，患有 DLBCL 的黑人患者被诊断的年龄比白人小 10 岁（平均年龄 53 岁对 70 岁），更有可能患有晚期疾病、没有保险或有医疗补助保险、居住在社会经济地位最低的地区，接受现代化疗的可能性较小。我们在第二个基于美国人口的数据集中证实了这些年龄和阶段的差异，并发现黑人的 5 年生存率也较差（38% 对 46%）。然而，在埃默里大学和阿拉巴马大学伯明翰分校 (UAB) 的单独研究以及我们的联合研究中，我们再次发现黑人患者的发病年龄明显更年轻，即使给予完全相同的治疗，生存率仍然较差。可以鉴定出两种生物学上不同的 DLBCL 亚型，它们具有不同的生存率：生发中心 B 细胞 (GCB) DLBCL：5 年生存率 60%，活化 B 细胞 (ABC) DLBCL：35%。我们建议研究这些生物学变异与 DLBCL 种族差异之间的关系。基于对 DLBCL 肿瘤和匹配正常组织中基因的广泛分析，我们帮助鉴定了 ABC 和 GCB DLBCL 中差异突变的 15 个基因，并试图确定这些基因是否因种族而异。主要目的是：1）检查 ABC 样 DLBCL 患病率的种族差异，并探讨 ABC 亚型、种族和生存之间的关系；2）检查 ABC 样 DLBCL 中差异突变的新基因的种族差异。我们从 Emory 和 UAB 队列研究中确定了 433 名 DLBCL 患者，并提供了可用的组织块和临床数据。我们正在收集人口、保险、就业、治疗、反应和生存数据，将构建组织微阵列，并将进行 IHC 亚型分析、突变和表达谱分析。公众健康相关性：弥漫性大 B 细胞淋巴瘤 (DLBCL) 是美国最常见的淋巴瘤，每年影响约 22,000 人。如果不及时治疗，几乎所有患者的寿命都不会超过一年，然而，通过现代化疗和抗体疗法的结合，超过 50% 的患者的淋巴瘤得到治愈，这使得 DLBCL 成为研究癌症差异的理想疾病。我们发现，患有 DLBCL 的黑人患者比白人更早被诊断出来，更有可能患有晚期疾病，并且即使给予相同的治疗，其生存率也较差，并且想要确定 DLBCL 的低风险生物亚型是否更容易出现这种情况。常见于黑人患者。