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

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.