Background

Much of what is known about cancer risk with AIDS is derived from the Branch's 20th century cohort studies of high risk populations and continuing U.S. HIV/AIDS Cancer Match. KS risk is closely tied to HIV-related cellular immune deficiency and to the secondary immunologic hyper-activation that occurs with HIV infection. The incidence of lymphomas, including Hodgkin as well as NHL, among people with HIV/AIDS varies greatly by histologic sub-type, suggesting that locally acting soluble factors contribute to the risk and the clinical manifestations. The varied risk of other malignancies with HIV/AIDS has generated new etiologic hypotheses and initiatives throughout the research community. IIB current activities build upon successful projects and utilize proven, state-of-the-art computer linkage tools and analytic methods.

HIV/AIDS Cancer Match, U.S.

People with AIDS are at extremely high risk of KS and NHL, and also are at elevated risk for Hodgkin lymphoma, cervical and anal cancer, lung cancer, and possibly other malignancies. By linking population-based AIDS and cancer registration data in 12 regions covering nearly half of the U.S. AIDS population, IIB has developed a powerful resource for assessment of cancer risk with AIDS and also with HIV prior to AIDS onset. It is essential for this resource to have relatively current data to detect changes in cancer incidence that reflect evolution of HIV treatment and demographic changes in the HIV/AIDS population (e.g., aging). To do so, the plan is to re-match one-third (four) of the regions each year (FY2007 through FY2010). Analyses, particularly by fellows, will include specific malignancies and populations on an ongoing basis. In FY2007, a pilot to collect covariate data from the HIV/AIDS registry population, for example on smoking, medication use, and comorbidities, has been proposed.

HIV/AIDS Cancer Match, International

In FY2006, linkage, analysis, and publication of data from Uganda were completed. In FY2007, IIB led a workshop in Mumbai, India, on HIV/AIDS cancer matching. During or shortly after this workshop, data on cancer and HIV/AIDS ascertainment will be evaluated and pilot studies to estimate the magnitude and types of cancer among people with HIV/AIDS in selected communities of India will be developed. Preliminary discussions for possible HIV/AIDS cancer matching in Thailand and South Africa will be continued. The overarching goal is to identify novel associations in populations with genetic backgrounds and exposures that differ greatly for those of the U.S.

EBV and Genetics in AIDS NHL

IIB has a pair of related projects to clarify the roles of EBV and common variants in genes controlling immunity and inflammation on the risk of AIDS-related NHL. In collaboration with the Multicenter AIDS Cohort Study (MACS), the interactions of EBV load, EBV cellular and humoral immunity, and variants in candidate genes are being studied in 181 incident lymphomas and matched controls. Then, to identify novel genetic associations, we plan to genotype 800 additional cases assembled from several sources with a haplotype-tagging panel of more than 150 genes on pathways implicated in lymphomagenesis.

Smoking and Pulmonary Dysplasia with HIV

Lung cancer risk is increased 3- to 5-fold among HIV-infected individuals. Modeling suggests that only part of this excess can be explained by frequent smoking, and it is possible that HIV-associated inflammation promotes smoking-induced lung carcinogenesis. To clarify these issues the Branch has proposed a series of cross-sectional studies within ALIVE, a prospective cohort of HIV-infected and -uninfected injection drug users in Baltimore, Maryland. In FY2007, urinary cotinine levels and detailed smoking data were measured. These results will be used to estimate whether smoking alone accounts for the lung cancer excess. If not, in FY2008-2009 HIV-infected and -uninfected drug users will be compared on prevalence and levels of biomarkers of exposure to tobacco carcinogens and tobacco-induced molecular mutations in sputum believed to be early diagnostic markers of lung cancer.

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