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：
8515358
负责人：
CHRISTOPHER R FLOWERS
金额：
$ 19.03万
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 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8515358
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 sequencing 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.

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，每年约22,000人。但是，如果未经治疗的DLBCL在1年内死亡，则使用化疗和免疫疗法的现代组合> 50％的患者可以治愈，这使DLBCL成为检查癌症差异的临床意义。我们发现，美国DLBCL的黑人患者被诊断出在十年岁的年龄比白人（平均年龄53岁对70岁）的年龄更大，更有可能患有预防疾病，没有保险或医疗补助保险，居住在最低的社会经济状况领域，并且不太可能接受现代化学疗法。我们确认了第二个基于美国人群的数据集的年龄和阶段差异，发现黑人的生存率也较差（38％比46％）。然而，在阿拉巴马大学 - 伯明翰大学（UAB）的单独研究和我们的合并研究中，我们再次发现，黑人患者的年龄较小，即使给予了完全相同的治疗，但生存率仍然较差。可以鉴定出具有不同生存率的两种生物学上不同的DLBCL亚型生存中心B细胞（GCB）DLBCL：60％5年生存和激活的B-Cell（ABC）DLBCL：35％。我们建议研究这些生物学变异与DLBCL中种族差异之间的关系。基于对DLBCL肿瘤中基因和匹配正常组织的基因的广泛分析，我们帮助鉴定了15种在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有所不同。主要目的是：1）检查类似ABC的DLBCL患病率的种族差异，并探索ABC亚型，种族和生存之间的关系，以及2），以检查在ABC样DLBCL中差异突变的新基因中的种族差异。我们通过可用的组织块和临床数据确定了来自Emory和UAB队列研究的433名DLBCL患者。我们正在收集人口统计学，保险，就业，治疗，响应和生存数据，将构建组织微阵列，并将执行IHC亚型，突变和表达分析。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Considerations in the initial management of follicular lymphoma.

DOI：
10.1016/j.cmonc.2012.09.015
发表时间：
2012-11-01
期刊：
Community oncology
影响因子：
0
作者：
Nastoupil L;Sinha R;Hirschey A;Flowers CR
通讯作者：
Flowers CR

New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy.

DOI：
10.1586/14737140.2015.1023712
发表时间：
2015-05
期刊：
Expert review of anticancer therapy
影响因子：
3.3
作者：
Chihara D;Nastoupil LJ;Williams JN;Lee P;Koff JL;Flowers CR
通讯作者：
Flowers CR

Examining racial differences in diffuse large B-cell lymphoma presentation and survival.

DOI：
10.3109/10428194.2012.708751
发表时间：
2013-02
期刊：
Leukemia & lymphoma
影响因子：
2.6
作者：
Flowers CR;Shenoy PJ;Borate U;Bumpers K;Douglas-Holland T;King N;Brawley OW;Lipscomb J;Lechowicz MJ;Sinha R;Grover RS;Bernal-Mizrachi L;Kowalski J;Donnellan W;The A;Reddy V;Jaye DL;Foran J
通讯作者：
Foran J

Evaluating cell-of-origin subtype methods for predicting diffuse large B-cell lymphoma survival: a meta-analysis of gene expression profiling and immunohistochemistry algorithms.