Biological Variants Underlying Racial Differences in Lymphoma

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。如果不治疗，92%的DLBCL在1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，使得DLBCL成为检查癌症差异的临床重要疾病。我们发现，在美国，黑人DLBCL患者的确诊年龄比白人小10岁（平均年龄53岁对70岁），他们更有可能处于疾病晚期，没有医疗保险或医疗补助，居住在社会经济地位最低的地区，接受现代化疗的可能性也更小。我们在第二个基于美国人群的数据集中证实了这些年龄和分期的差异，并发现黑人的5年生存率也更差（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，即使给予完全相同的治疗，黑人患者的年龄也明显更年轻，生存率仍然更低。生发中心b细胞（GCB） DLBCL的5年生存率为60%，活化b细胞（ABC） DLBCL的5年生存率为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，我们帮助鉴定了15个在ABC和GCB DLBCL中差异突变的基因，并试图确定这些基因是否因种族而异。主要目的是：1)研究ABC样DLBCL患病率的种族差异，探讨ABC亚型、种族与生存之间的关系；2)研究ABC样DLBCL新基因差异突变的种族差异。我们从Emory和UAB队列研究中确定了433名具有可用组织块和临床数据的DLBCL患者。我们正在收集人口统计、保险、就业、治疗、反应和生存数据，将构建组织微阵列，并将进行免疫组化分型、突变和表达谱分析。

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.