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Molecular determinants of lung cancer in HIV infected and uninfected individuals in Uganda and Tanzania

乌干达和坦桑尼亚艾滋病毒感染者和未感染者肺癌的分子决定因素

基本信息

批准号：
10267199
负责人：
STANTON L. GERSON
金额：
$ 31.24万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-21 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10267199
关键词：
Acceleration Address Adenocarcinoma Africa Africa South of the Sahara African Age Aging Biological Markers Blood Cells CD4 Positive T Lymphocytes Cancer Patient Cell Count Country DNA DNA Methylation Data Development Diagnosis Disease Disease Outcome Disease Progression Eastern Cooperative Oncology Group Environmental Risk Factor Epidemiologic Factors Epidemiology Equipment Future Genomics Genotype HIV HIV Infections HIV-1 Histology Home Image Immune Immunosuppression Incidence Individual Indoor Air Pollution Infection Institutes International Link Lung Capacity Malignant Neoplasms Malignant neoplasm of lung Measures Medical center Methylation Molecular Molecular Profiling Multivariate Analysis Mutation Mutation Analysis Pathologic Patients Performance Status Persons Policies Premature aging syndrome Psychological Transfer Relative Risks Reporting Risk Risk Factors Role Sampling Smoker Smoking Somatic Mutation South Africa Squamous cell carcinoma Tanzania Technology Tobacco smoking behavior Transference Tuberculosis Tyrosine Kinase Inhibitor Uganda University Hospitals Viral Load result Virus Diseases World Health Organization advanced disease antiretroviral therapy base cancer risk cohort cooking environmental tobacco smoke methylation pattern methylome prospective screening standard of care therapeutically effective

项目摘要

ABSTRACT – Project 2 We will assess molecular risks and co-incidence of lung cancer, HIV and accelerated aging as a factor in lung cancer incidence and progression in HIV infected patients. We will define the somatic mutations of lung cancer, link them to HIV subtype and explore the hypothesized role of DNA methylome aging in HIV- infected versus uninfected individuals as an associative factor that could potentially be utilized as a future biomarker to predict likelihood of lung cancer development or disease progression. These data will provide the first comprehensive assessment of somatic mutation burden in East African lung cancer, which will guide access to therapeutically effective agents to target actionable lung cancer mutations. These will be linked to risk factors associated with HIV including immunosuppression, immune protection, and accelerated aging that may increase the risk of cancer in HIV+ individuals. These will help to discern whether epidemiological factors from Project 1 can project risk for lung cancer at the molecular level and whether, together, we can identify prominent factors linking epidemiologic risk, HIV-1 infection, and lung cancer in East Africa.

摘要-项目2 我们将评估分子风险和肺癌，艾滋病毒和加速老化的共同发病率作为一个因素在肺 HIV感染患者的癌症发病率和进展。我们将定义肺癌的体细胞突变，将它们与HIV亚型联系起来，并探索DNA甲基化组老化在HIV感染者与未感染的个体作为一个关联因素，可能被用作未来的生物标志物，以预测肺癌发展或疾病进展的可能性。这些数据将提供第一个全面的评估东非肺癌的体细胞突变负担，这将指导获得治疗靶向可操作的肺癌突变的有效药剂。这些将与与以下相关的风险因素相关联：艾滋病毒包括免疫抑制，免疫保护和加速老化，可能会增加风险， HIV+患者的癌症。这些将有助于辨别项目1中的流行病学因素是否可以预测在分子水平上的肺癌风险，以及我们是否可以共同确定流行病学风险、HIV-1感染和东非肺癌。