Arsenic exposure, urinary arsenic speciation, and the incidence of urothelial carcinoma: a twelve-year follow-up study

The risk of urothelial carcinoma (UC) and urinary arsenic speciation have been evaluated in a few case–control studies; however, the association has not been verified in a prospective cohort study. The aim of this study was to examine the association between urinary arsenic speciation and the incidence of UC in a cohort study. A total of 1,078 residents of southwestern Taiwan were followed for an average of 12 years. A high-performance liquid chromatography/hydride generator and an atomic absorption spectrometry were used to measure urinary arsenite, arsenate, monomethylarsonic acid (MMA^V), and dimethylarsinic acid (DMA^V). The incidence of UC was estimated by examining the National Cancer Registry of Taiwan between January 1985 and December 2001. There were 37 newly diagnosed cases of UC during a follow-up period of 11,655 person-years. Significantly higher percentages of MMA^V and lower percentages of DMA^V existed among the patients with UC than among the healthy residents. After adjustment for age, gender, educational level, and smoking status, the percentage of urinary DMA^V was shown to have an inverse association with the risk of UC, having a relative risk (RR) of the tertile strata of 1.0, 0.3, and 0.3, respectively (p < 0.05 for the trend test). The RR (95% confidence interval) of residents with a cumulative arsenic exposure (CAE) of ≥20 mg/l-year and a higher percentage of MMA^V or a CAE of ≥20 mg/l-year and a lower percentage of DMA^V was 3.7 (1.2–11.6) or 4.2 (1.3–13.4) compared to residents with a CAE of <20 mg/l-year and a lower percentage of MMA^V or a CAE of <20 mg/l-year and a higher percentage of DMA^V respectively. There was a significant association between inefficient arsenic methylation and the development of UC in the residents in the high CAE exposure strata in an area of southwestern Taiwan endemic for arseniasis.