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.