Molecular epidemiology of infection-related cancer


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Charles Rabkin

Viral Epidemiology Branch, National Cancer Institute, USA

Abstract

Chronic infections cause up to 26% of cancers in developing countries and 8% in developed countries. The most numerous associations are with viruses, but several endemic bacteria and parasites also represent significant causes. The archetype of viral carcinogens is the ubiquitous Epstein-Barr virus, first isolated from Burkitts lymphoma over 40 years ago. Another herpesvirus may be a necessary cause of Kaposis sarcoma, but it has been difficult to determine whether this closely related virus is rare or common in the general population. The gradual disappearance of the bacterium Helicobacter pylori has been linked to declining rates of non-cardia gastric cancer, but paradoxically may be related to increasing incidence of lower esophageal and cardia cancer. A common feature of these varied agents is their propensity to persist in human hosts. Notably, the prevalence of the infections is generally orders of magnitude greater than the incidence of the associated cancers.

Thus, malignancy is an occasional result of the processes supporting infection persistence, but does not contribute to continuation of infection in the individual host nor the host population. The frequency of many - but not all - of these malignant outcomes may be increased with various states of immune compromise, including inherited immunodeficiencies, the acquired immunodeficiency syndrome (AIDS), iatrogenic immunosuppression, and perinatal acquisition. Oncogenic viruses tend to act by directly transforming tumor progenitor cells, inducing mutations, disrupting DNA homeostasis, or interfering with tumor suppressor pathways, for examples. In contrast, bacterial and parasitic carcinogens transform indirectly by affecting cellular processes, tissue turnover, and/or systemic systems that predispose to tumorigenesis, without being incorporated into the clonal tumor cell population.

Both mechanisms of action raise valuable prospects for intervention, through primary prevention of infection as well as by infection-directed treatment of disease. Further progress in molecular epidemiology should advance both understanding and control of infection-related cancer.