Vitamin D in viral associated lung cancers

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SUMMARY In recent years, the incidence of AIDS-defining cancers has dramatically decreased due to the highly active antiretroviral therapy (HAART). In contrast, the incidence of the non-AIDS-defining cancers (NADC), especially lung cancer (LC) has risen by more than 3 fold. In the U.S., LC has become the most common NADC with an incidence rate of 204 cases per 100,000 person-years. LC is also the most common NADC cause of death and accounts for 21% of cancer-related death in the human immunodeficiency virus (HIV)-infected population. Thus, there is an unmet need to understand the underlying mechanism of this deadly disease and develop more effective therapeutic strategy. Unlike other common HIV associated cancers such as cervical cancer, non-Hodgkin's lymphoma, and Kaposi's sarcoma, HIV associated LCs do not have an established viral etiology. Our parent R01 study (R01CA261258) shows that human papillomavirus (HPV) is causally associated with LCs in the HIV(+) population, which adds conceptually to our understanding of HIV associated LCs and provides potentially unique therapeutic opportunities. Based on strong preliminary evidence from both published literatures and our new experimental data, we now hypothesize that Vitamin D (VitD) as an important dietary nutrient plays a critical role in lung carcinogenesis in the HIV(+) population. In this administrative supplement, we propose to investigate VitD's anti-tumorigenic role and therapeutic potential for HIV associated LCs using our unique animal model system. We will examine an important concept of reversing the HIV/HAART-induced VitD insufficiency/deficiency by dietary VitD supplementation can improve the prognosis of HIV/HPV associated LCs. Successful completion of the supplement work can significantly enhance the parent R01 study by further elucidating the underlying mechanism of this lethal disease and ultimately benefit many HIV associated LC patients.