Arsenic metabolism and urothelial cancer risk: a systematic review and meta-analysis

Background Arsenic is a toxic metalloid element frequently found in the environment. Chronic arsenic exposure is a critical public health issue in many countries since the identification of arsenic and its compounds as human carcinogens by the World Health Organization. After absorption, inorganic arsenic (iAs) is mainly methylated into monomethylated and dimethylated compounds (MMA, DMA), which are then excreted through the kidney together with unmethylated iAs. Whether the methylation process is to detoxify or potentiate arsenic toxicity, however, remains an ongoing debate. The purpose of this systematic review was to conduct a comprehensive meta-analysis to estimate the association between arsenic exposure and urothelial cancer. Methods 10 observational studies met the inclusion criteria and were included in the systematic review. IAs%, MMA% and DMA% were extracted from each paper. Weighted Mean Differences with 95% confidence intervals were defined according to Cases minus Controls. Pooled risk estimates from individual studies were assessed using random effects models. Meta-regression analysis was performed to estimate the extent of urothelial cancer risk as a function of iAs%, MMA% and DMA%. Results Results showed as patients with urothelial cancer presented higher level of urinary iAs% (WMD 2.70, 95%CI 0.64-4.76), MMA% (WMD 2.81, 95%CI 1.43-4.20) and DMA% (WMD-3.44, 95%CI-6.57–0.30). Conclusions These findings suggest that higher level of iAs% and MMA% and lower level of DMA% were associated with an increased risk of urothelial cancer. Additional population based studies are needed to understand the role of arsenic in cancer development. Understanding the meaning of arsenic metabolism could improve the risk assessment of arsenic toxicity and provide a potential tool for disease prediction and prevention. Key messages Higher level of iAs%, MMA% and DMA% were associated with an increased risk of urothelial cancer. Understanding the meaning of arsenic metabolism could improve the risk assessment of arsenic toxicity.