Kaposi's sarcoma, oncogenic viruses, and iron

Introduction: Iron is required for many cellular processes, but it is also toxic in excess quantities. Therefore, iron homeostasis and utilization mus t be strictly maintained, and defects in iron absorption or transport resul t in iron depletion or accumulation. Most research has been directed to ent eral and placental transfer of iron, but little is known about iron entry t hrough the skin. We present evidence that exposure to wet clay soils in Afr ica is an important risk factor for Kaposi's sarcoma (KS) and speculate tha t iron may be responsible for soil toxicity contributing to the pathogenesi s of KS. Study design: Evidence gathered from case control studies and rela ted investigations in Uganda between 1995 and 1998 are summarized. Results: A large case control study of KS in HIV-infected adults disclosed affluenc e and mobility that suggest enhanced sexual exposure to humanherpesvirus-8. the putative aetiologic agent of KS. Another study in endemic KS (HIV-nega tive) also showed affluence and mobility as risk factors. In addition, bare foot exposure to wet soil was an important risk factor fur men with endemic KS. Other studies point to diminish delayed hypersensitivity in the lower limbs of KS patients. Geographic similarities of KS to podoconiosis (non-fi larial elephantiasis) in Africa implicate soil absorbtion through the skin in the pathogenesis of KS and podoconiosis. Conclusion: The hypothesis of s oil exposure as a risk for endemic KS has been strengthened by recent inves tigation. Particulate soil exposure may cause localized microtrauma and inf lammation. predisposing to KS on the extremities in HHV-8 infected men. A r ole for iron toxicity is yet to be determined. (C) 2001 Elsevier Science B. V. All rights reserved.