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Discovering the causes of cancer and the means of prevention

Classical Kaposi Sarcoma and KS Herpesvirus

The primary cause of KS is infection with KSHV, which is also known as human herpesvirus 8. AIDS KS has become the most common of all malignancies in areas of sub-Saharan Africa that have a high prevalence of both HIV and KSHV. In contrast, classical (non-AIDS) KS is rare, even in elderly Mediterranean populations that have KSHV seroprevalence above 10 percent. In case-control studies in Italy, we found that risk of cKS was significantly associated with  use of corticosteroid medications and especially with non-smoking. Null results in our randomized clinical trial of topical nicotine to treat cKS suggested that other, perhaps inflammation-related consequences of smoking may reduce cKS risk. We found that cKS was associated with polymorphisms in several immune-response genes, with deficient in vitro responses to KSHV peptides, and with deficient delayed-type hypersensitivity responses in the legs, where cKS usually originates. We recently found that cKS was associated with elevated plasma levels of  four of 70 immunity markers – soluble interleukin (sIL)-1 receptor II, sIL-2 receptor alpha, CC-chemokine ligand 3 (also known as MIP-1α), and especially CXC-chemokine ligand 10 (CXCL-10, also known as IP-10), which has been a focus of AIDS-KS treatment trials.  Analyses of HLA associations with cKS and with KSHV seropositivity are in progress.

For more information, contact James Goedert.

Infections and Immunoepidemiology Branch – Research Areas