title: Schistosome and liver fluke derived catechol-estrogens and helminth associated cancers.
abstract: Infection with helminth parasites remains a persistent public health problem in developing countries. Three of these pathogens, the liver flukes Clonorchis sinensis, Opisthorchis viverrini and the blood fluke Schistosoma haematobium, are of particular concern due to their classification as Group 1 carcinogens: infection with these worms is carcinogenic. Using liquid chromatography-mass spectrometry (LC-MS/MS) approaches, we identified steroid hormone like (e.g., oxysterol-like, catechol estrogen quinone-like, etc.) metabolites and related DNA-adducts, apparently of parasite origin, in developmental stages including eggs of S. haematobium, in urine of people with urogenital schistosomiasis, and in the adult stage of O. viverrini. Since these kinds of sterol derivatives are metabolized to active quinones that can modify DNA, which in other contexts can lead to breast and other cancers, helminth parasite associated sterols might induce tumor-like phenotypes in the target cells susceptible to helminth parasite associated cancers, i.e., urothelial cells of the bladder in the case of urogenital schistosomiasis and the bile duct epithelia or cholangiocytes, in the case of O. viverrini and C. sinensis. Indeed we postulate that helminth induced cancers originate from parasite estrogen-host epithelial/urothelial cell chromosomal DNA adducts, and here we review recent findings that support this conjecture.
authors.affiliation: Center for Parasite Biology and Immunology, National Health Institute Doutor Ricardo Jorge Porto, Portugal ; Center for the Study of Animal Science, Instituto de Ciências e Tecnologias Agrárias e Agroalimentares, University of Porto Porto, Portugal.
authors.forename: José M
authors.initials: JM
authors.lastname: Correia da Costa
authors.affiliation: Department of Chemistry and Biochemistry, Centro de Investigação em Química, University of Porto Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Vale
authors.affiliation: Center for the Study of Animal Science, Instituto de Ciências e Tecnologias Agrárias e Agroalimentares, University of Porto Porto, Portugal ; Department of Chemistry and Biochemistry, Centro de Investigação em Química, University of Porto Porto, Portugal.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Gouveia
authors.affiliation: Department of Health Promotion and Chronic Diseases, National Health Institute Doutor Ricardo Jorge Porto, Portugal.
authors.forename: Mónica C
authors.initials: MC
authors.lastname: Botelho
authors.affiliation: Tropical Disease Research Laboratory, Liver Fluke and Cholangiocarcinoma Research Center, Department of Pathology, Faculty of Medicine, Khon Kaen University Khon Kaen, Thailand.
authors.forename: Banchob
authors.initials: B
authors.lastname: Sripa
authors.affiliation: Experimental Pathology and Therapeutics Group, Portuguese Institute for Oncology of Porto Porto, Portugal.
authors.forename: Lúcio L
authors.initials: LL
authors.lastname: Santos
authors.affiliation: Center for the Study of Animal Science, Instituto de Ciências e Tecnologias Agrárias e Agroalimentares, University of Porto Porto, Portugal ; Experimental Pathology and Therapeutics Group, Portuguese Institute for Oncology of Porto Porto, Portugal.
authors.forename: Júlio H
authors.initials: JH
authors.lastname: Santos
authors.affiliation: Research Center for Neglected Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, George Washington University Washington, DC, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rinaldi
authors.affiliation: Research Center for Neglected Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, George Washington University Washington, DC, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
keywords: DNA-adducts; catechol-estrogens; cholangiocarcinoma; neglected tropical disease-associated-cancer; opisthorchiasis; oxysterols; squamous cell carcinoma of the bladder; urogenital schistosomiasis