GB Virus C and Non-Hodgkins Lymphoma Risk and Prognosis
GB C 病毒和非霍奇金淋巴瘤的风险和预后
基本信息
- 批准号:8438775
- 负责人:
- 金额:--
- 依托单位:
- 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:2012-10-01 至 2016-09-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAmino AcidsAnimal VirusesAntibodiesApoptosisB-Cell LymphomasB-LymphocytesBiologicalBloodBlood donorBlood donor screeningBritish ColumbiaCanadaCase-Control StudiesCell LineCell physiologyCellsCharacteristicsChronicClinicClinical ManagementClinical ResearchClinical SciencesCohort StudiesComorbidityDataDetectionDevelopmentDiagnostic testsDiseaseDonor SelectionEpidemiologic StudiesEvaluationEventFamilyFlaviviridaeFollicular LymphomaGB virus CGlycoproteinsGrantHealthHepatitis CHepatitis C virusHumanHuman VirusImmuneIn VitroIndividualInfectionLaboratoriesLymphocyteLymphomaMalignant NeoplasmsMeasurementMediatingMedicineNon-Hodgkin&aposs LymphomaNonstructural ProteinNorth AmericaOdds RatioPathogenicityPatientsPestivirusPhylogenyPlayPrevalenceProbabilityProteinsPublic HealthPublishingRNAReportingResearchResearch DesignRiskRisk FactorsRoleSamplingSouthern EuropeT-Cell LymphomaT-LymphocyteTestingTimeTransfusionVascular blood supplyViralViral ProteinsViremiaVirusVirus DiseasesWorkapoptosis in lymphocytesbaseblood productcase controlcohortcostdesignexperiencefollow-upin vivoinnovationlarge cell Diffuse non-Hodgkin&aposs lymphomanoveloutcome forecastpopulation basedprognosticprotein functionresearch studysuccess
项目摘要
DESCRIPTION (provided by applicant):
GB virus C (GBV-C) is a common human infection that, until recently, was not thought to be associated with any disease. Due to the perceived lack of pathogenicity, blood products are not screened for GBV-C, even though ~2% of U.S. blood donors are viremic at the time of donation. A recent large, Canadian, population-based case- control study found an association between GBV-C and non-Hodgkin lymphoma (NHL; odds ratio of 2.72 [95% CI 1.22-6.69]). Unfortunately, due to an imbalance in sample availability, the cases were not well matched with the controls. Nevertheless, previous studies, and several lines of evidence support biological plausibility for a relationship between GBV-C and NHL, the 6th most common cancer in the US. Specifically, GBV-C infection causes persistent infection of humans, replicates in B and T lymphocytes, prolongs survival of lymphocytes and is associated with delayed apoptosis in vivo and in vitro. Specifically, two viral proteins (nonstructural protein 5A and envelope glycoprotein E2) inhibit Fas-mediated apoptosis in lymphocyte cell lines. In addition, hepatitis C virus is an accepted risk for NHL, and GBV-C is closely related to HCV, sharing considerable amino acid homology (up to 80%) in several conserved nonstructural, replication-related proteins. In Specific Aim 1, we will determine whether GBV-C viremia is associated with the risk of developing NHL by using an existing clinic-based case-control study of 2500 cases and 2500 controls from the upper Midwestern US. In Aim 2 we will assess the relationship of past GBV-C infection (antibody positivity) on risk of NHL and prognosis, and in Aim 3 we will determine if GBV-C is associated with event-free and overall survival in NHL. As a secondary analysis, the association of GBV-C with NHL subtypes (diffuse large B cell lymphoma, other B-cell lymphomas, follicular lymphoma, or T cell lymphomas) will be examined, although power to assess subtype-specific associations was limited. This study fills a critical need to determine in an independent, rigorously-designed, and well-powered case-control study from North America whether GBV-C virus is associated with NHL risk and prognosis. Screening blood donors for GBV-C would be costly and require deferral of approximately 2% of donors. However, if GBV-C is associated with NHL, reconsideration of current blood donor screening testing would be necessary to protect the blood supply. By using an established case-control study cohort, for which the samples will be available at the start of this grant, and by working with leaders in GBV-C and lymphoma epidemiology and clinical research, the study has a high probability of success. The laboratory that will perform the GBV-C diagnostic testing developed the state-of-the-art approaches to be utilized, and has extensive published experience related to GBV-C research. The evaluation of a role for this virus in NHL prognosis is novel and innovative. Regardless of the results obtained, this study has the potential to have a great impact on public health regarding transfusion medicine, and potentially in the clinical management of NHL patients.
描述(由申请人提供):
GB病毒C(GBV-C)是一种常见的人类感染,直到最近才被认为与任何疾病无关。由于认为缺乏致病性,血液制品不进行GBV-C筛查,尽管约2%的美国献血者在献血时患有病毒血症。最近一项大型的加拿大人群病例对照研究发现GBV-C与非霍奇金淋巴瘤(NHL;比值比为2.72 [95% CI 1.22-6.69])之间存在相关性。不幸的是,由于样本可用性的不平衡,病例与对照组不匹配。尽管如此,之前的研究和多项证据支持GBV-C与NHL(美国第六常见癌症)之间关系的生物学合理性。具体而言,GBV-C感染导致人的持续感染,在B和T淋巴细胞中复制,破坏淋巴细胞的存活,并与体内和体外的延迟凋亡相关。具体而言,两种病毒蛋白(非结构蛋白5A和包膜糖蛋白E2)抑制Fas介导的淋巴细胞系凋亡。此外,丙型肝炎病毒是NHL的公认风险,GBV-C与HCV密切相关,在几种保守的非结构性复制相关蛋白中具有相当大的氨基酸同源性(高达80%)。在具体目标1中,我们将通过使用现有的基于临床的病例对照研究,确定GBV-C病毒血症是否与发生NHL的风险相关,该研究包括来自美国中西部上游的2500例病例和2500例对照。在目标2中,我们将评估既往GBV-C感染(抗体阳性)与NHL风险和预后的关系,在目标3中,我们将确定GBV-C是否与NHL的无事件生存期和总生存期相关。作为次要分析,将检查GBV-C与NHL亚型(弥漫性大B细胞淋巴瘤、其他B细胞淋巴瘤、滤泡性淋巴瘤或T细胞淋巴瘤)的相关性,尽管评估亚型特异性相关性的能力有限。这项研究填补了一个关键的需要,以确定在一个独立的,严格设计的,以及良好的病例对照研究,从北美是否GBV-C病毒与NHL的风险和预后。对献血者进行GBV-C筛查将是昂贵的,需要推迟大约2%的献血者。然而,如果GBV-C与NHL有关,则有必要重新考虑当前的献血者筛查测试,以保护血液供应。通过使用一个已建立的病例对照研究队列,其样本将在本基金开始时提供,并与GBV-C和淋巴瘤流行病学和临床研究的领导者合作,该研究成功的可能性很高。将进行GBV-C诊断检测的实验室开发了最先进的方法,并具有与GBV-C研究相关的广泛出版经验。评估这种病毒在NHL预后中的作用是新颖和创新的。无论获得的结果如何,这项研究都有可能对输血医学方面的公共卫生产生重大影响,并可能对NHL患者的临床管理产生重大影响。
项目成果
期刊论文数量(0)
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Jack T. Stapleton其他文献
Human antibody responses following vaccinia immunization using protein microarrays and correlation with cell-mediated and antibody dependent cellular cytotoxicity responses.
使用蛋白质微阵列进行痘苗免疫后的人类抗体反应以及与细胞介导和抗体依赖性细胞毒性反应的相关性。
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:6.4
- 作者:
S. Frey;Jack T. Stapleton;Z. Ballas;Wendy L Rasmussen;T. Kaufman;Tammy P Blevins;Travis L. Jensen;D. H. Davies;Magdalena Tary;Paul Chaplin;H. Hill;Johannes B. Goll;R. Belshe;Anna Wald;Christine Johnston;Lisa A. Jackson;Patricia L. Winokur;W. Keitel;Hana M El Sahly;R. Atmar;Shital M. Patel;S. El;Wilbur H. Chen;Srilatha Edupuganti;N. Rouphael;Mark J. Mulligan;Kathryn M. Edwards;C. B. Creech - 通讯作者:
C. B. Creech
Renaming of the genus Flavivirus to Orthoflavivirus and extension of binomial species names within the family Flaviviridae
- DOI:
10.1007/s00705-023-05835-1 - 发表时间:
2023-08-10 - 期刊:
- 影响因子:2.500
- 作者:
Thomas S. Postler;Martin Beer;Bradley J. Blitvich;Jens Bukh;Xavier de Lamballerie;J. Felix Drexler;Allison Imrie;Amit Kapoor;Galina G. Karganova;Philippe Lemey;Volker Lohmann;Peter Simmonds;Donald B. Smith;Jack T. Stapleton;Jens H. Kuhn - 通讯作者:
Jens H. Kuhn
Vaccination Success Rate and Reaction Profile With Diluted and Undiluted Smallpox Vaccine
稀释和未稀释天花疫苗的疫苗接种成功率和反应概况
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
Thomas R. Talbot;Jack T. Stapleton;R. C. Brady;Patricia L. Winokur;David I Bernstein;Teresa Germanson;Sandra M. Yoder;Kathryn M. Edwards - 通讯作者:
Kathryn M. Edwards
Hepatitis A virus attachment to cultured cell lines.
甲型肝炎病毒附着在培养的细胞系上。
- DOI:
- 发表时间:
1991 - 期刊:
- 影响因子:6.4
- 作者:
Jack T. Stapleton;John Frederick;Barbara Meyer - 通讯作者:
Barbara Meyer
Jack T. Stapleton的其他文献
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{{ truncateString('Jack T. Stapleton', 18)}}的其他基金
GB Virus C and Non-Hodgkins Lymphoma Risk and Prognosis
GB C 病毒和非霍奇金淋巴瘤的风险和预后
- 批准号:
8958794 - 财政年份:2012
- 资助金额:
-- - 项目类别:
GB Virus C and Non-Hodgkins Lymphoma Risk and Prognosis
GB C 病毒和非霍奇金淋巴瘤的风险和预后
- 批准号:
8768468 - 财政年份:2012
- 资助金额:
-- - 项目类别:
GB Virus C and Non-Hodgkins Lymphoma Risk and Prognosis
GB C 病毒和非霍奇金淋巴瘤的风险和预后
- 批准号:
8595173 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Characterization of cell GBV-C envelope glycoprotein interactions
细胞 GBV-C 包膜糖蛋白相互作用的表征
- 批准号:
8195612 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Characterization of cell GBV-C envelope glycoprotein interactions
细胞 GBV-C 包膜糖蛋白相互作用的表征
- 批准号:
8258626 - 财政年份:2009
- 资助金额:
-- - 项目类别:
The effects of hepatitis C virus (HCV) E2 protein on host immunomodulation
丙型肝炎病毒(HCV)E2蛋白对宿主免疫调节的影响
- 批准号:
8669712 - 财政年份:2009
- 资助金额:
-- - 项目类别:
The effects of hepatitis C virus (HCV) E2 protein on host immunomodulation
丙型肝炎病毒(HCV)E2蛋白对宿主免疫调节的影响
- 批准号:
8540646 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Novel viral immune interference mechanisms: HCV as a model system
新型病毒免疫干扰机制:HCV 作为模型系统
- 批准号:
9898211 - 财政年份:2009
- 资助金额:
-- - 项目类别:
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