Environmental and immunologic cofactors for the risk of classic Kaposi sarcoma in Sicily

Abstract

BACKGROUND: Cofactors for classic Kaposi's sarcoma (KS) are unclear and environmental and immunologic factors have been postulated. Using a case-control study in Sicily we examined the relationships between volcanic soil exposure, T-helper (Th) immune shift and classic KS in Sicily. METHODS: Histologically confirmed KS cases were identified through surveillance of Sicily's pathology laboratories. Population controls were selected using two-stage cluster sample design and KSHV seropositivity was determined for all subjects using 4 antibody assays. Classic KS cases (n=141) were compared to KSHV seropositive controls (n=123) on residential exposure to four types of soil, categorized with maps from the European Soil Database and direct surveying. A subset of plasma samples was tested for Epstein-Barr nuclear antigen (EBNA) and viral capsid antigen (VCA) antibodies, and for soluble cluster of differentiation sCD23, sCD26, and sCD30, as surrogate markers of Th1/Th2 immunity. Levels and categories of markers were compared between classic KS cases (n=119) and seropositive controls (n=105) to estimate odds of KS, and between the latter and seronegative controls (n=155) to estimate odds of KSHV seropositivity. RESULTS: Residents in communities rich in luvisols (iron rich soil) were approximately 2.7-times more likely to have classic KS than those in communities without luvisols. Among those in luvisol rich communities, the risk was elevated with frequent bathing or tap water drinking. Having KS was unrelated to living in communities high in andosols, tephra, or clay soils. EBV antibody and sCD levels did not differ between cases and seropositive controls, or between seropositive and seronegative controls. Low EBNA/high VCA antibody profile was not associated with KS or KSHV seropositivity. Among controls, subjects with the highest level of VCA antibodies were about twice as likely to be KSHV seropositive. EBV antibodies were lower among those with known KS risk factors, i.e.,male sex, nonsmoking, diabetes and cortisone use. CONCLUSION: Classic KS in Sicily is associated with living in area with luvisol rich soil, and water as a possible conduit should be investigated. Better methods are needed to assess possible associations of classic KS with Th1/Th2 immunity.