Why Does Infection With Some Helminths Cause Cancer?

Infections with Opisthorchis viverrini, Clonorchis sinensis, and Schistosoma haematobium are classified as group 1 biological carcinogens: definitive causes of cancer. These worms are metazoan eukaryotes, unlike the other group 1 carcinogens including human papilloma virus, hepatitis C virus, and Helicobacter pylori. By contrast, infections with phylogenetic relatives of these helminths, also trematodes of the phylum Platyhelminthes and major human pathogens, are not carcinogenic. These inconsistencies prompt several questions, including how might these infections cause cancer, and why is infection with only a few helminth species carcinogenic? We present an interpretation of mechanisms contributing to the carcinogenicity of these helminth infections, including roles for metabolites of catechol estrogen and oxysterols of parasite origin as initiators of carcinogenesis.