Low activity of dapsone N-hydroxylation as a susceptibility risk factor in aggressive bladder cancer

Pharmacogenetics. 1994 Aug;4(4):199-207. doi: 10.1097/00008571-199408000-00004.


N-arylamines involved in the pathogenesis of bladder cancer, require metabolic activation via N-hydroxylation. The efficiency of in vivo N-hydroxylation of dapsone, a non-carcinogenic arylamine, may, therefore, provide a host susceptibility measure of risk of developing bladder cancer. To investigate this possibility, the dapsone recovery ratio, a phenotypic measure of the efficiency of dapsone hydroxylation, has been measured in a case control study in an urban UK population, comparing patients with aggressive bladder cancer (n = 33), non-aggressive bladder cancer (n = 60) and controls (n = 108). Dapsone recovery ratio in controls exhibited a unimodal distribution. Patients with aggressive bladder cancer had a similar distribution but significantly lower mean value (p < 0.005). Logistic regression analysis, controlling for sex, age, smoking habit and alcohol consumption confirmed a significant (p < 0.05) association between the dapsone recovery ratio and aggressive bladder cancer. Subjects in the lowest tertile of dapsone recovery ratio had a relative risk to 5.4-fold greater than subjects in the upper tertile (p < 0.009), and a trends test was significant (p < 0.001). There was no significant association between dapsone recovery ratio and non-aggressive bladder cancer. These results do not support the hypothesis that the drug metabolizing enzymes involved in dapsone N-hydroxylation are involved in causing bladder cancer. Instead, they suggest the opposite, the observation that low enzyme activity was associated with increased risk is consistent with this enzyme providing a detoxification mechanism for environmental procarcinogens.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Case-Control Studies
  • Dapsone / metabolism*
  • Genetic Predisposition to Disease
  • Humans
  • Hydroxylation
  • Inactivation, Metabolic
  • Phenotype
  • Risk Factors
  • United Kingdom / epidemiology
  • Urinary Bladder Neoplasms / epidemiology*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology


  • Dapsone