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.José M. Correia da Costa, Maria J. Gouveia, Mónica C.
Botelho, Lúcio L. Santos, and Júlio H. Santos thank FCT for
Pest- OE/AGR/UI0211/2011 and Strategic Project UI211-2011-
2013, Clínica Sagrada Esperança and Hospital Américo Boavida,
Luanda, Angola. Nuno Vale thanks to Fundação para a Ciência
e Tecnologia (FCT, Portugal) and FEDER (European Union) for
funding through project grants CONCREEQ/275/QUI and PEstC/QUI/UI0081/2011.
Nuno Vale also thanks FCT for Post-Doc
grant SFRH/BPD/48345/2008. The research findings reviewed
here were supported by award R01CA155297 (Paul J. Brindley,
Gabriel Rinaldi, Banchob Sripa) from the National Cancer Institute,
NIH and P50 P50AI098639 (Banchob Sripa, Paul J. Brindley)
from the National Institute of Allergy and Infectious Diseases,
NIH