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: 8175390
• 负责人: SAM M MBULAITEYE
• 金额: $ 222.05万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8175390
• 关键词: Acquired Immunodeficiency Syndrome; Adolescent; Adrenal Cortex Hormones; Adult; Age; Alleles; Anus; Biological; Biological Assay; Biological Markers; Breast; Bronchi; Burkitt Lymphoma; CD4 Lymphocyte Count; Cancer Etiology; Case-Control Studies; Categories; Cause of Death; Cells; Cessation of life; Childhood; Clinical; Cohort Studies; Collaborations; DNA Nucleotidylexotransferase; Data; Dermal; Detection; Development; Diabetes Mellitus; Diagnosis; Disease; Epidemiology; Extramural Activities; Fostering; Genetic Variation; HIV; Haplotypes; Head and Neck Cancer; Hepatitis C virus; Hodgkin Disease; Human; Human Herpesvirus 8; Human T-lymphotropic virus 1; Incidence; Infection; Infectious Agent; Interleukin-10; Island; Kaposi Sarcoma; Laboratories; Larynx; Link; Liver; Lung; Lymphoma; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of lung; Malignant neoplasm of penis; Malignant neoplasm of testis; Measures; Merkel Cells; Merkel cell carcinoma; Methods; Natural History; Neurodegenerative Disorders; Neuroendocrine Cell; Non-Burkitt' s Lymphoma; Non-Hodgkin' s Lymphoma; Oncornaviruses; Oral cavity; Organ Transplantation; Persons; Pharyngeal structure; Polyomavirus; Population; Proteins; Registries; Research; Retinoblastoma Genes; Risk; Risk Factors; Role; Saliva; Satellite Viruses; Sicily; Smoking; Soil; Specimen; Staining method; Stains; TP53 gene; Tissue Microarray; Tongue; Tumor Tissue; Viral; Viral Load result; Virus; base; cancer risk; cohort; malignant breast neoplasm; malignant stomach neoplasm; mortality; multidisciplinary; neoplastic cell; penis; peripheral blood; population based; prospective; transmission process; tumor; volcano

This project consists of several overlapping comprehensive, multidisciplinary population-based cohort and/or case-control studies to quantify the association between cancer-causing viruses (oncoviruses) with linked cancers. The studies focus on the role of the role of immunological alteration, infection and risk for cancer, including BL, NHL, Hodgkin lymphoma, kaposi sarcoma, lung cancer, cervical cancer, head and neck cancer, testicular cancer, breast cancer, penile cancer, and gastric cancer. Biological specimens (peripheral blood, saliva, tumor tissues), when available, are used to measure load of infectious agents, including HIV, HTLV-I/-II, HCV, and KSHV, also called HHV8, genetic variation in viral agents or the host to characterize association of biomarkers with cancer. Using the U.S. HIV/AIDS Cancer Match Study, among 567, 865 persons with HIV/AIDS, BL incidence showed two age-specific incidence peaks during the pediatric and adult/geriatric years and decreased with decreasing CD4 lymphocyte counts. The bimodal peaks for BL, in contrast to non-BL NHL, suggest effects of non-cumulative risk factors at different ages. In US registry-based cohort of 83,282 people with AIDS (1980-2006), overall mortality decreased from 302 deaths per 1000 person-years in 1980-1989, to 140 deaths per 1000 person-years in 1990-1995, and to 29 deaths per 1000 person-years in 1996-2006. AIDS-defining cancer related mortality decreased from 2.95 deaths per 1000 person-years in 1980-1989 to 0.65 deaths per 1000 person-years in 1996-2006, but the fraction of AIDS-defining cancer -related deaths increased from 1.05% to 2.47% in association with decreases in other AIDS-related deaths. NHL was the most common cancer-related cause of death (36% of deaths during 1996-2006) and lung cancer was the most common non-AIDS-defining cancer cause of death (21% of cancer-related deaths in 1996-2006). In US registry-based cohort of 83,282 people with AIDS (1980-2006), overall mortality decreased from 302 deaths per 1000 person-years in 1980-1989, to 140 deaths per 1000 person-years in 1990-1995, and to 29 deaths per 1000 person-years in 1996-2006. AIDS-defining cancer related mortality decreased from 2.95 deaths per 1000 person-years in 1980-1989 to 0.65 deaths per 1000 person-years in 1996-2006 , but the fraction of AIDS-defining cancer -related deaths increased from 1.05% to 2.47% in association with decreases in other AIDS-related deaths. NHL was the most common cancer-related cause of death (36% of deaths during 1996-2006) and lung cancer was the most common non-AIDS-defining cancer cause of death (21% of cancer-related deaths in 1996-2006). Using data from 263 254 adults and adolescents with AIDS (1980-2004) the U.S. HACM, we showed that risk was elevated for the 2 major AIDS-defining cancers: Kaposi sarcoma (SIRs, 5321 and 1347 in years 3-5 and 6-10, respectively) and non-Hodgkin lymphoma (SIRs, 32 and 15) and for all non-AIDS-defining cancers combined (SIRs, 1.7 and 1.6 in years 3-5 and 6-10, respectively) and for Hodgkin lymphoma and cancers of the oral cavity and/or pharynx, tongue, anus, liver, larynx, lung and/or bronchus, and penis. A four-year case-control study of classic (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. Classic KS also was increased with residential exposure chromic luvisols, a soil associated with volcanoes. Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. We developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06-1.2 viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (p < or = 0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis and longer survival (p < or = 0.08). Using data from the Multicenter AIDS Cohort Study (MACS), we showed that carriage of at least one copy of the T allele for the IL10 rs1800871 (as compared to no copies) was associated with decreased AIDS-NHL risk specific to lymphomas arising from the CNS (CC vs. CT/TT: OR = 0.3; 95% CI 0.1, 0.7) but not systemically (CC vs. CT/TT: OR = 1.0; 95% CI 0.5, 1.9) (Pheterogeneity = 0.03). Carriage of two copies of the 'low IL10' haplotype rs1800896_A/rs1800871_T/rs1800872_A was associated with decreased lymphoma risk that varied by number of copies (Ptrend = 0.02). Collaborations with private and academic laboratories were established to foster development of detection methods for known or possible cancer-associated viruses.

该项目包括几个重叠的综合，多学科的基于人群的队列和/或病例对照研究，以量化引起癌症的病毒（Oncovires）与链接的癌症之间的关联。该研究重点是免疫学改变，感染和癌症风险的作用，包括BL，NHL，Hodgkin淋巴瘤，Kaposi肉瘤，肺癌，宫颈癌，头颈癌，睾丸癌，乳腺癌，阴茎癌，阴茎癌和胃癌。生物学标本（外周血，唾液，肿瘤组织）（如果可用）可用来测量传染剂的负荷，包括HIV，HTLV-I/-II，HCV和KSHV，也称为HHV8，也称为HHV8，病毒药物或宿主的遗传变异，以表征生物标志物与癌症的生物标志物相关。 使用美国艾滋病毒/艾滋病癌症匹配研究，在567名艾滋病毒/艾滋病患者中，BL的发生率在儿科和成人/老年幼年期间显示出两个特定年龄的发病率峰，并且随着CD4淋巴细胞计数的降低而减少。与非BL NHL相比，BL的双峰峰表明，不同年龄在不同年龄的非肿瘤风险因素的影响。在基于美国注册表的83,282名艾滋病人群（1980-2006）中，总死亡率从1980 - 1989年的每1000人年死亡的302人减少到1990 - 1995年的每1000人年死亡人数140人，到1996 - 2006年的每1000人死亡29人。定义癌症相关的死亡率从1980 - 1989年的每1000人年死亡的2.95人减少到1996 - 2006年的每1000人年死亡人数的0.65例，但与其他艾滋病相关的死亡减少的艾滋病相关死亡的比例从1.05％增加到2.47％。 NHL是与癌症有关的最常见的死亡原因（1996- 2006年死亡的36％），肺癌是最常见的定义癌症死亡原因（1996- 2006年与癌症相关的死亡的21％）。 在基于美国注册表的83,282名艾滋病人群（1980-2006）中，总死亡率从1980 - 1989年的每1000人年死亡的302人减少到1990 - 1995年的每1000人年死亡人数140人，到1996 - 2006年的每1000人死亡29人。定义癌症相关的死亡率从1980 - 1989年的每1000人年死亡的2.95人减少到1996 - 2006年的每1000人年死亡人数的0.65例，但与其他艾滋病相关的死亡减少的艾滋病相关死亡的比例从1.05％增加到2.47％。 NHL是与癌症有关的最常见的死亡原因（1996- 2006年死亡的36％），肺癌是最常见的定义癌症死亡原因（1996- 2006年与癌症相关的死亡的21％）。 使用来自263254名成年人和青少年的数据（1980-2004），美国HACM，我们表明，定义2个主要艾滋病癌症的2个主要艾滋病的风险升高：卡波西肉瘤（SIRS，5321和1347年，分别为3-5和6-10年），以及非hodgkin lymphoma（sirs sirs and cans and-nrend cans and 32 and 32和32和15） （分别为3 - 5年和6-10年的SIRS，1.7和1.6）以及霍奇金淋巴瘤和口腔淋巴瘤和癌症和/或咽，舌头，舌头，肛门，肝脏，肝，喉，肺和/或支气管以及阴茎。整个西西里岛的经典（非AID）Kaposi肉瘤和KSHV感染的四年病例对照研究完成（CKS和KSHV是地方性的）。当前吸烟随着糖尿病和使用皮质类固醇的使用而显着且独立增加，经典的KS风险大大降低了。经典KS也随着与火山相关的土壤而增加的住宅暴露铬luvisols也增加了。最近在默克尔细胞癌（MCC）中发现了默克尔细胞多瘤病毒（MCPYV），这是皮肤神经内分泌细胞的临床和病理异质性恶性肿瘤。我们开发了组织微阵列（TMA），以表征候选肿瘤细胞蛋白的免疫组织化学染色和定量PCR分析，以检测MCPYV并测量病毒载量。在23个（74％）的原发性MCC肿瘤中有19个（74％）中检测到MCPYV，但其中8个每300个细胞的病毒拷贝少于1个病毒拷贝。病毒丰度为0.06-1.2病毒拷贝/细胞直接与视网膜母细胞瘤基因产物（PRB）和末端脱氧核糖核苷酸转移酶（TDT）的存在直接相关（P <或= 0.003）。较高的病毒丰度肿瘤往往与p53表达较小，诊断年龄较小和生存期更长有关（P <OR = 0.08）。使用来自多中心艾滋病队列研究（MAC）的数据，我们表明，在IL10 rs1800871（与无副本相比）中，至少运输了T等位基因的至少一份T等位基因的副本与CNS引起的淋巴瘤的降低相关（CC VS. vs. vs.ct/tt/tt; ct/tt; 95％CI; 95％ci; 95％ci; 95％ci; 95％ci; CT/TT：OR = 1.0; 95％CI 0.5，1.9）运输“低IL10”单倍型RS1800896_A/RS1800871_T/RS1800872_A的两份副本与淋巴瘤风险降低相关，这会随副本数量而变化（Ptrend = 0.02）。 建立了与私人和学术实验室的合作，以促进已知或可能与癌症相关病毒的检测方法的开发。