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）：世界上近百分之二十的癌症负担可归因于慢性传染病。大多数与感染相关的癌症已被证明具有病毒病因，尽管细菌和寄生虫也造成了全球癌症负担。所有已知的与病毒相关的癌症在免疫抑制个体中都会特别增加，并且还有其他癌症可能具有病毒病因，因为它们在免疫抑制后也会增加。淋巴瘤、肛门生殖器恶性肿瘤和肺癌在多种免疫抑制个体中越来越常见。我们建议在此应用中确定最有可能归因于感染的那些癌症的病毒病因。具体来说，我们将重点关注在免疫抑制个体中更常见但与 Epstein Barr 病毒（霍奇金淋巴瘤和弥漫性大 B 细胞淋巴瘤）相关性不一致的淋巴瘤子集，近 50% 的阴茎癌和外阴癌与 Epstein Barr 病毒相关。未归因于人乳头瘤病毒（HPV）感染，以及吸烟有限的年轻免疫抑制人群中的多种肺癌。我们的总体策略是从多个免疫抑制人群中显着增加的癌症中获取样本，对肿瘤转录组进行高通量测序和计算分析来识别病毒序列，开发检测方法来确定病毒是否通常与癌症相关。记录病例对照系列，并开始以默克尔细胞多瘤病毒（MCPyV）为例研究病毒致癌机制。我们汇集了一支在癌症生物学、传染病、病毒发现、计算生物学和流行病学方面具有互补专业知识的研究人员团队，他们将能够获得源自乌干达艾滋病毒感染者的独特肿瘤标本，并在艾滋病毒阴性乌干达人中进行验证和来自美国的移植队列。