Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
基本信息
- 批准号:7733733
- 负责人:
- 金额:$ 583.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AIDS/HIV problemAcquired Immunodeficiency SyndromeAdrenal Cortex HormonesAdultAgeAllelesAnemiaAntibodiesB-LymphocytesBCL6 geneBiochemicalBiological AssayBloodBlood Coagulation FactorBlood PlateletsBreastBurkitt LymphomaCD4 Lymphocyte CountCD4 Positive T LymphocytesCUL5 geneCX3CL1 geneCXCL12 geneCalendarCase-Control StudiesCategoriesCellsCellularityClinicalClonalityCohort StudiesCollaborationsComplexConjunctival Squamous Cell CarcinomaCyclophilin ADataData AnalysesDetectionDevelopmentDiabetes MellitusDiagnosisDiseaseEnrollmentEpidemicEpidemiologyExtramural ActivitiesFamilyFosteringGenderGene ExpressionGenesGenotypeGoalsHIVHIV-1HLA Class I GenesHTLV-1 InfectionHaplotypesHead and Neck CancerHemoglobinHemophilia AHepatitis B VirusHepatitis CHepatitis C virusHispanicsHodgkin DiseaseHomosexualsHumanHuman Herpesvirus 8Human T-lymphotropic virus 1HypersensitivityIL18 geneIL4 geneIL4R geneImmunityImmunologic Deficiency SyndromesImmunosuppressionIncidenceIndividualInfectionInfectious AgentInflammationInterleukin-10Interleukin-13Interleukin-4IslandJamaicaKaposi SarcomaLaboratoriesLactate DehydrogenaseLactate DehydrogenasesLesionLiverLymphocyteLymphomaMalignant NeoplasmsMalignant neoplasm of cervix uteriMalignant neoplasm of lungMalignant neoplasm of penisMalignant neoplasm of testisMethodsMulticenter Hemophilia Cohort StudyNatural HistoryNeuraxisNeurodegenerative DisordersNicotineNon-Hodgkin&aposs LymphomaNormal CellOrgan TransplantationParticipantPatternPersonsPopulationProceduresProvirusesRANTESRadiationRandomized Clinical TrialsRateRegistriesRelative (related person)Relative RisksResearchRiskRoleSamplingSatellite VirusesSclerosisSicilySingle Nucleotide PolymorphismSmokeSpinal Cord DiseasesT-LymphocyteTSG101 geneTestingTherapeutic immunosuppressionTimeVariantViolaViral Load resultVirusWeekWomanY Chromosomebasecancer riskcase controlcohorteosinophilfollow-uphuman CX3CR1 proteinhuman leukocyte antigen genelarge cell Diffuse non-Hodgkin&aposs lymphomaleukemia/lymphomamalignant breast neoplasmmalignant stomach neoplasmmenmultidisciplinaryneoplastic cellperipheral bloodprospectivetransmission processtrend
项目摘要
This project is a comprehensive, multidisciplinary effort to understand the natural history and modes of transmission of viruses and other infectious agents that are associated with cancer. With numerous intramural and extramural laboratory, clinical, and epidemiologic collaborators, and a core of prospective cohort and case-control studies, the effort is focused on human immunodeficiency virus (HIV), human T-lymphotropic virus types I and II (HTLV-I/-II), hepatitis C virus (HCV), and Kaposi sarcoma-associated herpesvirus (KSHV, also called human herpesvirus 8 or HHV-8). The Second Multicenter Hemophilia Cohort Study (MHCS-II) enrolled and completed prospective follow-up of more than 2500 HCV-exposed persons with hemophilia. A public website was established (https:mhcs-ii.rti.org) with background information and data analysis procedures. Progression of HIV/AIDS was shown to be associated with variants in several immunity-related genes (HLA/KIR, cyclophilin A, RANTES, CX3CR1), and likelihood of hepatitis B virus (HBV) clearance was associated with variants in IL10 and IL20. Among HIV-uninfected participants, spontaneous clearance of HCV was found to be associated with infection at a very young age and in relatively recent calendar years. In collaboration, AIDS progression rate was related to differences in several genes related to immunity. The hepatitis C virus (HCV) epidemic in the U.S. hemophilia population was reconstructed, revealing that most infections occurred prior to use of clotting factor concentrates. Spontaneous clearance of HCV infection was shown to be greatly increased with hepatitis B virus (HBV) co-infection. In addition, among hemophiliacs without HIV, HCV clearance also was clustered in families and increased with early age at infection. An HBV viral load assay was developed, and clearance of HBV was related to variants in the IL-18 gene. Progression of HIV/AIDS was shown to be associated with variants in several immunity-related genes (CUL5, cyclophilin A, TSG101, and HLA/KIR), and new methods were developed to analyze these complex relationships. A four-year case-control study of classical (non-AIDS) Kaposi sarcoma and KSHV infection throughout the island of Sicily (where cKS and KSHV are endemic) was completed. Classic KS risk was significantly reduced with current smoking, and it was significantly and independently increased with diabetes and use of corticosteroids. KS transdermal nicotine trial " A 15-week randomized clinical trial was completed, showing that use of transdermal patches to directly deliver nicotine to classic KS lesions was neither harmful nor beneficial. Among HTLV-I-infected people in Jamaica, common variants in HLA Class I genes were associated with a significantly increased risk of adult T-cell leukemia/lymphoma (ATL) and with non-significantly increased levels of HTLV-I proviral load. Common HLA variants were not related to HTLV-associated myelopathy. In a study comparing HTLV-1 carriers with HTLV-1 negative subjects, markers of HTLV-1 infection (infection status, antibody titer, and provirus load) were associated with hematologic and biochemical alterations, such as lymphocyte abnormalities, anemia, decreased eosinophils, and elevated lactate dehydrogenase levels. Using the the U.S. HIV/AIDS Cancer Match Study, study of human immunodeficiency virus (HIV)-infected persons with modest immunosuppression, before the onset of acquired immunodeficiency syndrome (AIDS), demonstrated elevated risk for Kaposi sarcoma (KS, SIR 1,300), non-Hodgkin lymphoma (NHL, 7.3), cervical cancer (2.9) and several non-AIDS-defining malignancies, including Hodgkin lymphoma (5.6 ) and cancers of the lung (2.6 ) and liver (2.7). Non-AIDS-defining cancers comprised 31.4% of cancers in 1991-1995, versus 58.0% in 1996-2002. In a study of cancer risk in the 4-27 month period following AIDS diagnosis, KS incidence was lower in 1996-2002 (335/ 100,000 person-years) than in 1990-1995 (1839/100,000 person-years), NHL incidence pattern was similar (i.e., 390/100,000 person-years in 1996-2002 and 1066/100,000 person-years in 1990-1995). In 1996-2002, for each decline in CD4 cell count of 50 cells per microliter of blood, KS risk increased by 40%, central nervous system non-Hodgkin lymphoma subtypes by 85%, diffuse large B-cell lymphoma 12%, but n increases were demonstrable for Burkitt lymphoma . Kaposi sarcoma (RR = 0.22, 95% CI = 0.20 to 0.24) and for non-Hodgkin lymphoma (RR = 0.40, 95% CI = 0.36 to 0.44) risks were lower in the period of 1996-2002 than in 1990-1995. In persons with HIV/AIDS (PWHAs), the risk of Hodgkin lymphoma (HL) 4 through 27 months after AIDS onset was significantly higher in 1996 to 2002 than earlier. The incidence in PWAs with 150 to 199 CD4 cells/muL was 53.7 per 10(5) py's, whereas in PWAs with fewer than 50 CD4 cells/muL, it was 20.7 per 10(5) py's (P(trend) = .002). For each HL subtype, incidence decreased with declining CD4 counts, but nodular sclerosing decreased more precipitously than mixed cellularity, thereby increasing the proportion of mixed cellularity HL seen in PWAs. The extent standardized incidence ratio (SIR) may underestimate relative risk (RR) of cancer risk among people with HIV/AIDS (PWHA) in registry-based was investigated using the 3 AIDS-related cancers: KS, central nervous system non-Hodgkin lymphoma (CNS NHL) and cervical cancer. SIRs substantially underestimate RRs for KS and CNS NHL, likely from the exceptionally high relative risk of KS and CNS NHL among PWHA. The risk for squamous cell carcinoma of the conjunctiva (SCCC) was observed to be increased in persons with AIDS (SIR, 12.5; 95% CI 7.0 - 20.6) using data from the US HIV/AIDS cancer match study. The relative proportion of was higher among Hispanics and among individuals residing in regions with high ambient ultra violet (u.v.) radiation supporting a role for immunosuppression in SCCC genesis. Risk was unrelated to gender, HIV exposure category, CD4 lymphocyte count, and time relative to AIDS-onset. For HIV/AIDS lymphomas, an analysis of 179 incident lymphomas and matched controls among HIV-1-seropositive homosexual men in the Multicenter AIDS Cohort Study (MACS). Subjects were genotyped for single nucleotide polymorphisms (SNPs) in B-cell stimulatory (IL10, IL10RA, CXCL12, CCL5), allergy-related (IL13, IL4, IL4R) and inflammation-related (BCL6) genes. Compared to the "high IL10" genotype -592CC, carriers of the IL10-592A allele were at lower risk of NHL, and the putative "low-producer IL10" haplotype, -1082A/-819T/-592A was less frequent in cases than controls (16% vs 22%, P=0.03). None of other studied genes differed significantly between cases and controls. Using samples from the KS clonality and gene expression study, we tested the hypothesis that whole KS cells can be transmitted sexually was examined in 25 women by looking for presence of Y-chromosome in KS tumor cells as compared to normal cells. None were positive. Data on human herpesvirus 8 load in peripheral blood has been analyzed and shown to be associated with KS progression and, to a lesser extent, with KS burden. Other correlates include low hemoglobin and low platelets. Collaborations with private and academic laboratories were established to foster development of detection methods for known or possible cancer-associated viruses.
该项目是一项全面的、多学科的工作,旨在了解与癌症相关的病毒和其他传染源的自然历史和传播模式。凭借众多校内和校外实验室、临床和流行病学合作者以及前瞻性队列和病例对照研究的核心,我们的工作重点是人类免疫缺陷病毒 (HIV)、人类 T 淋巴细胞病毒 I 型和 II 型 (HTLV-I) I-II)、丙型肝炎病毒 (HCV) 和卡波西肉瘤相关疱疹病毒 (KSHV,也称为人类疱疹病毒 8 或 HHV-8)。第二次多中心血友病队列研究 (MHCS-II) 入组并完成了对 2500 多名 HCV 暴露的血友病患者的前瞻性随访。建立了一个公共网站(https:mhcs-ii.rti.org),提供背景信息和数据分析程序。 HIV/AIDS 的进展与多种免疫相关基因(HLA/KIR、亲环蛋白 A、RANTES、CX3CR1)的变异相关,乙型肝炎病毒 (HBV) 清除的可能性与 IL10 和 IL20 的变异相关。在未感染艾滋病毒的参与者中,发现丙型肝炎病毒的自发清除与很小的时候和最近几年的感染有关。通过合作,艾滋病进展率与几个与免疫相关的基因的差异有关。重建了美国血友病人群中的丙型肝炎病毒 (HCV) 流行情况,揭示了大多数感染发生在使用凝血因子浓缩物之前。乙型肝炎病毒 (HBV) 合并感染后,HCV 感染的自发清除率大大增加。此外,在没有艾滋病毒的血友病患者中,丙型肝炎病毒的清除率也集中在家庭中,并且随着感染时年龄的增长而增加。开发了 HBV 病毒载量测定法,HBV 的清除与 IL-18 基因的变异有关。 HIV/AIDS 的进展与多种免疫相关基因(CUL5、亲环蛋白 A、TSG101 和 HLA/KIR)的变异有关,并且开发了新方法来分析这些复杂的关系。一项针对整个西西里岛(cKS 和 KSHV 流行)的经典(非艾滋病)卡波西肉瘤和 KSHV 感染的为期四年的病例对照研究已经完成。当前吸烟可显着降低典型 KS 风险,而糖尿病和使用皮质类固醇则可显着且独立地增加该风险。 KS 透皮尼古丁试验“一项为期 15 周的随机临床试验已完成,表明使用透皮贴剂直接将尼古丁递送至经典 KS 病变既无害也无益处。在牙买加 HTLV-I 感染者中,HLA 类常见变异I 基因与成人 T 细胞白血病/淋巴瘤 (ATL) 风险显着增加相关,并且与 HTLV-I 前病毒载量水平非显着增加相关。 HLA 变异与 HTLV 相关脊髓病无关。在一项比较 HTLV-1 携带者与 HTLV-1 阴性受试者的研究中,HTLV-1 感染标志物(感染状态、抗体滴度和原病毒载量)与血液学和生化改变相关。 ,例如淋巴细胞异常、贫血、嗜酸性粒细胞减少和乳酸脱氢酶水平升高。使用美国艾滋病毒/艾滋病癌症匹配研究(人类免疫缺陷研究)。在获得性免疫缺陷综合症(艾滋病)发病之前,患有轻度免疫抑制的病毒(HIV)感染者患卡波西肉瘤(KS,SIR 1,300)、非霍奇金淋巴瘤(NHL,7.3)、宫颈癌(2.9)的风险升高以及几种非艾滋病定义的恶性肿瘤,包括霍奇金淋巴瘤(5.6)和肺癌(2.6) )和肝脏(2.7)。 1991-1995 年,非艾滋病定义的癌症占癌症的 31.4%,而 1996-2002 年这一比例为 58.0%。在一项关于艾滋病诊断后 4-27 个月内癌症风险的研究中,1996-2002 年 KS 发病率(335/100,000 人年)低于 1990-1995 年(1839/100,000 人年),NHL 发病率模式相似(即 390/100,000 人年) 1996-2002年和1990-1995年1066/10万人年)。 1996-2002年,每微升血液中CD4细胞计数每下降50个细胞,KS风险增加40%,中枢神经系统非霍奇金淋巴瘤亚型增加85%,弥漫性大B细胞淋巴瘤增加12%,但n伯基特淋巴瘤的增加是明显的。 1996-2002 年期间卡波西肉瘤(RR = 0.22,95% CI = 0.20 至 0.24)和非霍奇金淋巴瘤(RR = 0.40,95% CI = 0.36 至 0.44)的风险低于 1990-1995 年。在艾滋病毒/艾滋病患者 (PWHA) 中,1996 年至 2002 年艾滋病发病后 4 至 27 个月内患霍奇金淋巴瘤 (HL) 的风险明显高于之前。在具有 150 至 199 个 CD4 细胞/μL 的 PWA 中,发病率为每 10(5) py 53.7 例,而在 CD4 细胞少于 50 个/μL 的 PWA 中,发病率为每 10(5) py 20.7 例 (P(趋势) = .002 )。对于每种 HL 亚型,发病率随着 CD4 计数的下降而下降,但结节性硬化比混合细胞性下降更急剧,从而增加了 PWA 中看到的混合细胞性 HL 的比例。在基于登记的艾滋病毒/艾滋病患者 (PWHA) 中,使用 3 种与艾滋病相关的癌症:KS、中枢神经系统非霍奇金淋巴瘤,对标准化发病率 (SIR) 的程度可能低估了癌症风险的相对风险 (RR) (中枢神经系统非霍奇金淋巴瘤)和宫颈癌。 SIR 大大低估了 KS 和 CNS NHL 的 RR,这可能是因为 PWHA 中 KS 和 CNS NHL 的相对风险异常高。根据美国 HIV/AIDS 癌症匹配研究的数据,艾滋病患者患结膜鳞状细胞癌 (SCCC) 的风险增加(SIR,12.5;95% CI 7.0 - 20.6)。西班牙裔和居住在高环境紫外线 (u.v.) 辐射地区的个体中的相对比例较高,支持免疫抑制在 SCCC 发生中的作用。风险与性别、HIV 暴露类别、CD4 淋巴细胞计数以及艾滋病发病相关时间无关。对于 HIV/艾滋病淋巴瘤,对多中心艾滋病队列研究 (MACS) 中 HIV-1 血清阳性男同性恋者中的 179 例淋巴瘤和匹配对照进行了分析。对受试者的 B 细胞刺激基因(IL10、IL10RA、CXCL12、CCL5)、过敏相关基因(IL13、IL4、IL4R)和炎症相关基因(BCL6)的单核苷酸多态性 (SNP) 进行基因分型。与“高 IL10”基因型 -592CC 相比,IL10-592A 等位基因携带者患 NHL 的风险较低,而假定的“低产生 IL10”单倍型 -1082A/-819T/-592A 的病例发生率低于对照(16% vs 22%,P=0.03)。其他研究的基因在病例和对照之间没有显着差异。使用 KS 克隆性和基因表达研究的样本,我们通过与正常细胞相比,在 KS 肿瘤细胞中寻找 Y 染色体的存在,在 25 名女性中检验了整个 KS 细胞可以通过性传播的假设。没有一个呈阳性。外周血中人类疱疹病毒 8 负荷的数据已被分析,并显示其与 KS 进展相关,并且在较小程度上与 KS 负荷相关。其他相关因素包括低血红蛋白和低血小板。与私人和学术实验室建立了合作,以促进已知或可能的癌症相关病毒检测方法的开发。
项目成果
期刊论文数量(20)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa.
冈比亚肝癌研究:乙型肝炎和丙型肝炎感染以及西非患肝细胞癌的风险。
- DOI:
- 发表时间:2004-01
- 期刊:
- 影响因子:0
- 作者:Kirk, Gregory D;Lesi, Olufunmilayo A;Mendy, Maimuna;Akano, Aliu O;Sam, Omar;Goedert, James J;Hainaut, Pierre;Hall, Andrew J;Whittle, Hilton;Montesano, Ruggero
- 通讯作者:Montesano, Ruggero
IL1B polymorphisms and gastric cancer risk.
IL1B 多态性与胃癌风险。
- DOI:
- 发表时间:2007-03
- 期刊:
- 影响因子:0
- 作者:Camargo, M Constanza;Mera, Robertino;Correa, Pelayo;Peek Jr, Richard M;Piazuelo, M Blanca;Sicinschi, Liviu;Schneider, Barbara G;Zabaleta, Jovanny;Fontham, Elizabeth T H;Goodman, Karen J;Ryckman, Kelli K
- 通讯作者:Ryckman, Kelli K
Infection with human herpes virus type 8 in an area at high prevalence for hepatitis C virus infection in southern Italy.
意大利南部丙型肝炎病毒感染高发地区发生 8 型人类疱疹病毒感染。
- DOI:
- 发表时间:2004-05
- 期刊:
- 影响因子:2.5
- 作者:Montella, M;Serraino, D;Crispo, A;Romano, N;Fusco, M;Goedert, J J
- 通讯作者:Goedert, J J
A case-control study of cancer of the uterine cervix in Uganda.
乌干达宫颈癌的病例对照研究。
- DOI:
- 发表时间:2007-12
- 期刊:
- 影响因子:0
- 作者:Newton, Robert;Ziegler, John;Casabonne, Delphine;Beral, Valerie;Mbidde, Edward;Carpenter, Lucy;Maxwell Parkin, D;Wabinga, Henry;Mbulaiteye, Sam;Jaffe, Harold;Uganda Kaposi's Sarcoma Study Group
- 通讯作者:Uganda Kaposi's Sarcoma Study Group
BK virus and cancer in Uganda.
乌干达的 BK 病毒和癌症。
- DOI:
- 发表时间:2006-08
- 期刊:
- 影响因子:0
- 作者:Newton, Robert;Ribeiro, Tatiana;Alvarez, Eva;Ziegler, John;Casabonne, Delphine;Carpenter, Lucy;Beral, Valerie;Mbidde, Edward;Parkin, Donald Maxwell;Wabinga, Henry;Mbulaiteye, Sam;Jaffe, Harold;Touze, Antoine;Coursaget, Pierre;Uganda Kaposi's
- 通讯作者:Uganda Kaposi's
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SAM M MBULAITEYE其他文献
SAM M MBULAITEYE的其他文献
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{{ truncateString('SAM M MBULAITEYE', 18)}}的其他基金
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
8565441 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
10263752 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
10702928 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
8763628 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
10918985 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
10007424 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
8938248 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
7966670 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
8349578 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
Epidemiology and Natural History of Cancer-Associated Viruses
癌症相关病毒的流行病学和自然史
- 批准号:
9549618 - 财政年份:
- 资助金额:
$ 583.39万 - 项目类别:
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