[Frontiers in Bioscience 14, 3455-3464, January 1, 2009]

Infectious agents and human malignancies

John L. Ziegler1, Franco M. Buonaguro2

1University of California-San Francisco, San Francisco, California 94143-0808, USA, 2Molecular Biology and Viral Oncogenesis, Department of Experimental Oncology, Istituto Nazionale Tumori, Fond, G, Pascale, 80131 Napoli, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Cancer pathways
2.2. Oncogenesis
2.3. Cancer and inflammation
2.4. Tumour immunity
3. Infectious agents and cancer: Evidence for causality
3.1. Epstein Barr virus (EBV)
3.2. Kaposi's sarcoma herpes virus (KSHV)
3.3. Hepatitis B Virus (HBV) and hepatitis C virus (HCV)
3.4. Human papillomavirus (HPV)
3.5. Helicobacter pylori
3.6. Human immunodeficiency virus (HIV)
3.7. Schistosoma haematobium
3.8. Mucosa-associated lymphoid tissue (MALT) lymphoma
3.9. Human T-cell lymphotropic virus (HTLV-1)
4. Perspective
5. References

1. ABSTRACT

Cancer has periodically been proposed as transmissible disease in animals and humans, and specific pathogens have long been searched for. Several biomolecular studies, fundamental in understanding cancer pathogenesis, have identified mechanisms directly/indirectly involved in pathogens-related cancer, including 1) oncogene transduction, with introduction of exogenous oncogenic genes; 2) activation of endogenous oncogenes, comprising those from endogenous retroviruses; 3) inactivation of constitutive suppressor genes, with enhanced susceptibility to exogenous oncogenic agents. Further pathogens' indirect role is associated to cancer promotion through inflammation and angiogenesis. The global burden of cancer associated with infectious agents approaches 20% of all malignancies. Most of the common "infectious" cancers occur in developing countries and their "attributable risk" (i.e. the proportion of cancers that would not occur if the agent were removed) is considerable. Although the cancer role of often ubiquitous pathogens, and the molecular mechanisms involved in the infrequent progression of chronic infections to cancers are still often unknown, the identity of the agents and efforts to mitigate their effects can lead to effective cancer prevention and substantive public health benefit.