Novel Pathogen Associated Cancers (PQ12)

新型病原体相关癌症 (PQ12)

基本信息

批准号：
8550028
负责人：
Corey Casper
金额：
$ 73.64万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
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：
2012-09-24 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8550028
关键词：
Anogenital cancer Antiviral Agents Bacteria Biological Assay Cancer Biology Cancer Burden Capsid Proteins Cause of Death Cells Chronic Clonality Collection Communicable Diseases Computational Biology Computer Analysis DNA DNA Viruses Early Diagnosis Epidemiology Etiology Exposure to Gene Expression Profile Genes Goals HIV HIV Infections HIV Seropositivity Hepatitis B Vaccines Hodgkin Disease Human Human Herpesvirus 4 Human Papilloma Virus Vaccine Human Papillomavirus Immunocompromised Host Immunosuppression In Situ Hybridization Individual Infection Institutes Link Liver Lymphoma Malaria Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of penis Malignant neoplasm of vulva Merkel Cells Molecular Non-Small-Cell Lung Carcinoma Oncogene Proteins Oncogenes Oncogenic Open Reading Frames Parasites Pathway interactions Patients Penis carcinoma Polyomavirus Population Property Protein p53 Proteins RNA library Research Personnel Retroviridae Sampling Satellite Viruses Series Serological Seroprevalences Small T Antigen Specimen Technology Testing Tobacco Transplant Recipients Transplantation Tuberculosis Uganda United States Validation Viral Viral Genome Viral Tumor Antigens Virus Vulva Carcinoma cancer prevention cancer type carcinogenesis case control cohort experience immunosuppressed infection related cancer killings large cell Diffuse non-Hodgkin&apos s lymphoma novel novel virus pathogen prevent public health relevance response tumor tumorigenesis viral RNA viral carcinogenesis

项目摘要

DESCRIPTION (provided by applicant): Nearly twenty percent of the world's cancer burden can be attributed to chronic infectious diseases. Most infection-associated cancers have been shown to have a viral etiology, though bacteria and parasites also contribute to the global cancer burden. All known virus-associated cancers are specifically increased among immunosuppressed individuals, and there are other cancers that likely have a viral etiology because they too are increased following immunosuppression. Lymphoma, anogenital malignancies and lung cancer have been found to be increasingly common in a diverse set of immunosuppressed individuals. We propose to identify a viral etiology of those cancers most likely attributable to infection in this application. Specifically, we will focus on the subset of lymphomas that are more common in immunosuppressed individuals but have not been consistently related to Epstein Barr Virus (Hodgkin lymphoma and diffuse large B-cell lymphoma), the nearly 50% of penile and vulvar cancers that have not been attributed to infection with human papillomavirus (HPV), and a wide variety of lung cancers in a young immunosuppressed population with limited exposure to tobacco. Our overall strategy will be to obtain samples from cancers that are significantly increased in multiple immunosuppressed populations, to perform high throughput sequencing of tumor transcriptomes and computational analyses to identify viral sequences, to develop assays to determine whether the viruses are generally associated with cancers using well documented case-control series, and to begin to investigate the mechanisms of viral carcinogenesis using Merkel Cell polyomavirus (MCPyV) as an example. We bring together a team of investigators with complementary expertise in cancer biology, infectious diseases, virus discovery, computational biology and epidemiology, which will have access to unique tumor specimens originating from individuals with HIV infection in Uganda as well as validation in HIV-negative Ugandans and transplant cohorts from the United States.

描述（由申请人提供）：世界上近20％的癌症负担可以归因于慢性传染病。尽管细菌和寄生虫也会导致全球癌症负担，但大多数与感染相关的癌症已被证明具有病毒病因。在免疫抑制个体中，所有已知的病毒相关癌症都会明确增加，并且其他一些癌症可能具有病毒病因，因为免疫抑制后它们也增加了。淋巴瘤，肛门生态恶性肿瘤和肺癌在多种免疫抑制个体中越来越普遍。我们建议确定最有可能归因于此应用中感染的癌症的病毒病因。具体而言，我们将重点关注在免疫抑制个体中更常见的淋巴瘤的子集，但并未始终与爱泼斯坦巴尔病毒（Hodgkin淋巴瘤和弥漫性大B细胞淋巴瘤）相关，该阴茎和外阴癌的近50％与人类Papphillomavirus（Hpillomavirus can Cancers can Cancers can Cancers）（均未归因于Hepillomavirus can Cancers），并且免疫抑制人群，暴露于烟草的人群有限。我们的整体策略将是从多种免疫抑制人群中显着增加的癌症的样品，以进行肿瘤转录组和计算分析的高吞吐量测序以识别病毒序列，以开发试验，以确定病毒通常与癌症使用良好的病例对照系列的癌症相关，并开始使用can cansement seremir of callir callir callir callir callir carrir carcirir carcirs carcir carcirs carcirs carcirs carcirs carcirs carcirs carcinisgirs，并且一个例子。我们将一组研究人员组合在一起，在癌症生物学，传染病，病毒发现，计算生物学和流行病学方面具有互补的专业知识，该团队将获得源自乌干达艾滋病毒感染的人以及HIV阴性的乌干达人和来自美国艾滋病毒的人群的验证的独特肿瘤标本。