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

Tumour Biol. 2017 Mar;39(3):1010428317692247. doi: 10.1177/1010428317692247.

Abstract

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.

Keywords: Schistosoma haematobium; bladder; estrogen-DNA adduct; estrogen-like metabolites; squamous cell carcinoma; urogenital schistosomiasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / pathology*
  • DNA Adducts / genetics
  • Estradiol / metabolism*
  • Humans
  • Reactive Oxygen Species / metabolism
  • Schistosoma haematobium / metabolism*
  • Schistosomiasis haematobia / parasitology*
  • Schistosomiasis haematobia / pathology*
  • Tumor Suppressor Protein p53 / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / parasitology

Substances

  • DNA Adducts
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • Estradiol