Arsenic metabolism and cancer risk: A meta-analysis

Objective: To describe the studies that have reported association measures between risk of cancer and the percentage distribution of urinary inorganic arsenic (iAs) metabolites by anatomical site, in non-ecological epidemiological studies. Methods: Studies were identified in the PubMed database in the period from 1990 to 2015. Inclusion criteria were: non-ecological epidemiological study, with histologically confirmed cancer cases, reporting the percentage distribution of inorganic arsenic (iAs), monomethylated (MMA) and dimethylated (DMA) metabolites, as well as association measures with confidence intervals (CI) between cancer and %iAs and/or %MMA and/or %DMA. A descriptive meta-analysis was performed by the method of the inverse of the variance for the fixed effects model and the DerSimonian and Laird's method for the random effects model. Heterogeneity was tested using the Q statistic and stratifying for epidemiological design and total As in urine. The possibility of publication bias was assessed through Begg's test. Results: A total of 13 eligible studies were found, most of them were performed in Taiwan and focused on skin and bladder cancer. The positive association between %MMA and various types of cancer was consistent, in contrast to the negative relationship between %DMA and cancer that was inconsistent. The summary risk of bladder (OR =1.79; 95% CI: 1.42, 2.26, n = 4 studies) and lung (OR = 2.44; 95% CI: 1.57, 3.80, n=2 studies) cancer increased significantly with increasing %MMA, without statistical heterogeneity. In contrast, lung cancer risk was inversely related to %DMA (OR= 0.58; 95% CI: 0.36, 0.93, n =2 studies), also without significant heterogeneity. These results were similar after stratifying by epidemiological design and total As in urine. No evidence of publication bias was found. Conclusion: These findings provide additional support that methylation needs to be taken into account when assessing the potential iAs carcinogenicity risk.