Biological Variants Underlying Racial Differences in Lymphoma

描述(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。如果没有治疗，92%的DLBCL患者在一年内死亡，然而，随着现代化疗和免疫治疗的结合，50%的患者被治愈，使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的黑人患者被确诊的年龄比白人年轻10岁(平均年龄53岁对70岁)，更有可能患有晚期疾病，没有保险或医疗补助保险，居住在社会经济地位最低的地区，并且不太可能接受现代化疗。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上的差异，发现黑人的5年存活率也更差(38%比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，黑人患者出现的年龄要年轻得多，即使给予完全相同的治疗，他们的存活率仍然更低。DLBCL有两种不同的生物学亚型，具有不同的存活率，生发中心B细胞(GCB)DLBCL的5年存活率为60%，活化的B细胞(ABC)DLBCL的存活率为35%。我们建议研究这些生物变异与DLBCL的种族差异之间的关系。基于对DLBCL肿瘤和匹配的正常组织中基因的广泛分析，我们帮助确定了15个在ABC和GCB DLBCL中发生差异突变的基因，并试图确定这些基因是否因种族而不同。主要目的是：1)检测ABC样DLBCL患病率的种族差异，探讨ABC亚型、种族和生存之间的关系；2)检测ABC样DLBCL中差异突变的新基因的种族差异。我们从Emory和UAB队列研究中利用可用的组织块和临床数据确定了433名DLBCL患者。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、突变和表达谱分析。 公共卫生相关性：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。然而，如果不治疗，几乎所有患者的寿命都不到一年，然而，通过现代化疗和抗体治疗的组合，超过50%的患者的淋巴瘤被治愈，这使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，即使给予同样的治疗，生存也更差，并想要确定DLBCL的低风险生物学亚型是否在黑人患者中更常见。

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.