Interaction between environmental tobacco smoke and arsenic methylation ability on the risk of bladder cancer

Cancer Causes Control. 2005 Mar;16(2):75-81. doi: 10.1007/s10552-004-2235-1.


Objective: Arsenic exposure and environmental tobacco smoke (ETS) have been suspected to be associated with bladder cancer risk. We hypothesize that interaction between ETS and the ability to methylate arsenic, a detoxification pathway, modifies the risk of bladder cancer.

Methods: From January 1996 to December 1999, we identified 41 newly diagnosed bladder cancer patients and 202 fracture and cataract patients at the National Cheng-Kung University (NCKU) Medical Center. The levels of urinary arsenic species [As(III), As(V), MMA(V), and DMA(V)] were determined in all subjects.

Results: We found significant interaction between ETS and secondary methylation index (SMI) on the risk of bladder cancer (p=0.02). Among non-smokers with a high primary methylation index (PMI), the risk of bladder cancer was lower in subjects exposed to ETS (OR, 0.37; 95% CI, 0.14-0.96) than in subjects without exposure to ETS. Among non-smokers without ETS, the risk of bladder cancer was 4.7 times higher in subjects with a low SMI (95% CI, 1.30-16.81) than in subjects with a high SMI.

Conclusions: Ability to methylate arsenic plays an important role in reducing the risk of bladder cancer attributable to the continuation of arsenic exposure from drinking water and from ETS exposure.

Publication types

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

MeSH terms

  • Aged
  • Air Pollutants / adverse effects
  • Air Pollutants / pharmacokinetics
  • Air Pollutants / urine
  • Arsenic / adverse effects
  • Arsenic / pharmacokinetics*
  • Arsenic / urine
  • Carcinoma, Transitional Cell / urine
  • Case-Control Studies
  • Cataract / urine
  • Environmental Pollutants / adverse effects
  • Environmental Pollutants / pharmacokinetics*
  • Environmental Pollutants / urine
  • Female
  • Fractures, Bone / urine
  • Humans
  • Inactivation, Metabolic
  • Male
  • Methylation
  • Middle Aged
  • Risk Factors
  • Sex Factors
  • Smoking / urine
  • Taiwan
  • Tobacco Smoke Pollution / adverse effects*
  • Urinary Bladder Neoplasms / etiology*
  • Urinary Bladder Neoplasms / urine
  • Water Pollutants, Chemical / adverse effects
  • Water Pollutants, Chemical / pharmacokinetics
  • Water Pollutants, Chemical / urine


  • Air Pollutants
  • Environmental Pollutants
  • Tobacco Smoke Pollution
  • Water Pollutants, Chemical
  • Arsenic