Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence

Abstract

Background: Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework.

Methods: Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size.

Results: Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2-4.1]; 4.2 [2.1-6.3] and; 5.8 [2.9-8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35-4.0], 2.3 [0.59-6.4], and 3.1 [0.80-8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L.

Conclusion: Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial.

Figure 1

Study selection process. Note that several studies report on more than one cancer site.

Figure 2

Arsenic concentrations from studies reporting on urinary tract cancers outcomes and arsenic exposure in drinking water. † indicates studies reporting significant associations and square brackets indicates citation number. Studies included in the meta-analysis are shown with an asterisk (*). Of the 40 studies reviewed, 3 used biomarkers to measure As exposure [51,94,95] and 2 failed to provide a specific measure of As-concentration [28,37].

Figure 3

Published risk estimates for varying levels of arsenic in drinking water in relation to bladder and kidney cancer mortality (A-B) and bladder cancer incidence (C). Solid lines show the predicted risk from the model fitted values obtained from meta-analyses; referent study for analyses is in bold; R² is the coefficient of determination based upon best fit to distributional assumption. RRs were all adjusted for tobacco smoking. Citation for original publication is in square brackets.

Figure 4

Distribution of predicted cancer risk estimates (A-B: mortality rates for bladder and kidney cancers; C: standardized mortality ratio for bladder cancer; D: incident relative risk for bladder cancer) at three levels of arsenic concentrations (10, 50 and 150 μg/L) in drinking water. Distributions were obtained from a bootstrap randomization of the fixed effects arsenic-risk models which were parameterized as a function of logged arsenic and the study from which the data were derived. A total of 10,000 randomizations were used.