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

摘要 – 项目 2 我们将评估肺癌、艾滋病毒和加速衰老作为肺癌影响因素的分子风险和同时发生率 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，并探讨 DNA 甲基化老化在 HIV 感染者与 HIV 感染者中的假设作用 未感染个体作为关联因素，有可能用作未来的生物标志物来预测 肺癌发生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 针对可操作的肺癌突变的有效药物。这些将与相关的风险因素有关 HIV 包括免疫抑制、免疫保护和加速衰老，这些可能会增加感染风险 艾滋病毒个体的癌症。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 肺癌在分子水平上的风险，以及我们是否可以共同确定与肺癌相关的重要因素 东非的流行病学风险、HIV-1 感染和肺癌。

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.