Abstract
Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous cell carcinoma (SCC) of the urinary bladder, respectively [2]. By contrast, infection with phylogenetic relatives, also trematodes of the phylum Platyhelminthes and also major pathogens, is not carcinogenic. These irregularities suggest that either helminth-specific metabolites contribute to tumorigenesis and/or that certain tissues or organs are particularly susceptible to infection-induced malignancy. Moreover, each of these helminth infections must be viewed holistically in the context of a perfect storm of risk for cancer (see [3]).
Highlights
In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) and squamous cell carcinoma (SCC) of the urinary bladder, respectively [2]
The mechanism(s) by which infection initiates genetic lesions that eventually culminate in CCA is not understood, it is likely to be multifactorial, involving biliary tract and systemic chronic inflammation and associated endogenous nitrosation [6, 7], secretion of mitogens and other mediators by the parasite, and cofactors including dietary preferences for nitrosamines-rich foods [4, 8, 9] (Fig 1)
Three major species of schistosomes are the agents of schistosomiasis: S. japonicum and S. mansoni cause intestinal schistosomiasis whereas S. haematobium causes urogenital schistosomiasis
Summary
Citation: Brindley PJ, Loukas A (2017) Helminth infection–induced malignancy. PLoS Pathog 13(7): e1006393. https://doi.org/10.1371/journal. ppat.1006393 Funding: AL acknowledges support from NHMRC via a Senior Principal Research Fellowship, project and program grants. Support from the National Institute of Allergy and Infectious Diseases (NIAID), Tropical Medicine Research Center award number P50AI098639, and the National Cancer Institute (NCI) award number R01CA164719 is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.
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