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

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。

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.