Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis-associated bladder cancer

Gouveia, Maria João; Santos, Jorge; Brindley, Paul J.; Rinaldi, Gabriel; Lopes, Carlos; Santos, Lúcio Lara; Costa, José Manuel Correia da; Vale, Nuno

doi:10.1016/j.canlet.2015.01.018

Cited by 56 publications

(86 citation statements)

References 52 publications

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“…Nitrosamines and increased levels of urinary b-glucuronidase and cyclooxygenase-2 derived from adult schistosomes are also recognized as bladder carcinogens. A liquid chromatography-mass spectrometry analysis of urine samples from UGS patients revealed numerous estrogen-like metabolites including catechol estrogen quinones (CEQ), CEQ-DNA-adducts and novel metabolites derived from 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG) (Gouveia et al, 2015). The detection of 8-oxodG indicates the damage of DNA in UGS via oxidative stress as the formation of 8-oxodG is known as a main product of DNA lesion by oxidation.…”

Section: Schistosomiasis and Cancermentioning

confidence: 99%

Parasite Infection, Carcinogenesis and Human Malignancy

et al. 2017

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Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

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Section: Schistosomiasis and Cancermentioning

confidence: 99%

Parasite Infection, Carcinogenesis and Human Malignancy

et al. 2017

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“…Cholesterol, oxysterols and estrogens are closely related steroids [58]. Oxysterols and catechol-estrogens occur in both O. viverrini and S. haematobium [29, 30, 47, 59]. Formation of these metabolites might relate to the physiology of the worms and/or parasite-host interactions implicated in metabolic pathways of steroid hormones and bile acids.…”

Section: Catechol Estrogens and Oxysterols From Helminth Parasites Asmentioning

confidence: 99%

Why Does Infection With Some Helminths Cause Cancer?

2015

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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? Here we present an interpretation of mechanisms contributing to the carcinogenicity of these helminth infections, including roles for catechol estrogen- and oxysterol-metabolites of parasite origin as initiators of carcinogenesis.

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“…Furthermore, these phenomena may explain formation of 8-oxodG derivatives (as illustrated in Figure 4), metabolites known from urine during UGS. 15 …”

Section: Consequences Of Estrogen-like Metabolitesmentioning

confidence: 99%

“…The probability of this phenomenon ultimately depends on the mutagenesis pressure on the target tissue that in the context of UGS where the described estrogen-like metabolites are produced may be higher. 15 …”

Section: Overexpression Of P53 During Ugsmentioning

confidence: 99%

“…11 Estrogen-DNA adduct-mediated pathways may underlie, at least partly, the etiopathogenesis of the UGS-induced bladder cancer. [12][13][14][15][16] Interactions between the estrogen receptor (ER) and total antigen preparation of S. haematobium have been described in vitro. Chinese Hamster Ovary (CHO) cells transfected with a construct expressing luciferase driven by the estrogen response element (ERE) were exposed to S. haematobium adult worm antigen preparation.…”

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The role of estradiol metabolism in urogenital schistosomiasis-induced bladder cancer

et al. 2017

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Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasis-induced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these metabolites emphasizing their potential effects on the dysregulation of the tumor suppressor gene p53 expression during urogenital schistosomiasis. Enhanced understanding of these potential carcinogens may not only shed light on urogenital schistosomiasis-induced neoplasia of the bladder, but would also facilitate development of interventions and biomarkers for this and other infection-associated cancers at large.

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Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis-associated bladder cancer

Cited by 56 publications

References 52 publications

Parasite Infection, Carcinogenesis and Human Malignancy

Parasite Infection, Carcinogenesis and Human Malignancy

Why Does Infection With Some Helminths Cause Cancer?

The role of estradiol metabolism in urogenital schistosomiasis-induced bladder cancer

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