Arsenic Exposure Is Associated with Significant Upper Tract Urothelial Carcinoma Health Care Needs and Elevated Mortality Rates

Arsenic exposure in Northern Chile: Antofagasta is located in the Atacama Desert, one of the aridest regions worldwide. Sources of water for consumption are scarce and originate from underground aquifers, leaching arsenic and other minerals as they flow downslope through the Andes Mountains. Until the 1950s, drinking water in the region met criteria considered acceptable for those times. However, in 1958, the waters of the Toconce river were captured using a 300 km piping system in order to satisfy the increasing demands of drinking water in this flourishing mining region. The latter caused an abrupt increase in mean arsenic concentrations in drinking water from around 90 to about 900 mg/L, exposing the population to levels up to 17 times higher than those recommended by the World Health Organization (WHO) at that time. Unfortunately, the need to support population and economic growth made the authorities to overlook potential risks related to arsenic exposure. Efforts to reduce arsenic started only over 10 years later. In 1970, a water treatment plant with adequate technology was installed, leading to significant drops in arsenic concentrations. Thereafter, a series of changes incorporating new cleaner sources up in the Andes and the modernization of the water supply network led to sustained reductions on arsenic levels, reaching WHO recommended levels by 1990.

Meanwhile, chronic exposure to arsenic in drinking water led to a series of health-related problems, including increases in infant mortality, skin lesions, nervous system disorders, respiratory diseases, and myocardial infarction; along with lung, bladder and nonmelanoma skin cancers.

What makes the scenario of Antofagasta's exposure to arsenic unique is the single source of drinking water for the whole region, where arsenic concentrations have been systematically measured since the 1950s. The entire population was exposed to known arsenic concentrations for a known period. In contrast, in other exposed regions (e.g. Taiwan), water comes from multiple wells with high variations on arsenic concentrations. This fact makes Antofagasta an ideal scenario to assess the risks of exposure to arsenic using non-experimental studies. In our research, we used an ecological approach, being case-control and cohort studies other options to investigate this association.

Arsenic-related urothelial carcinoma: The association of arsenic and bladder cancer has been well studied, establishing a clear dose-dependent risk profile. The relation with upper tract urothelial carcinoma (UTUC) is less clear, as many studies have included UTUC along with renal cell cancer (RCC). Consequently, two different entities with entirely different etiologies and behaviors were considered as one, diluting the magnitude of the effect of arsenic in UTUC. In fact, by selecting only UTUC cases and separating them from RCC, Ferrechio et al.¹ showed a significant increase in incidence while our study showed a significant increase in specific mortality. Interestingly, the magnitude of this association is much stronger than for bladder cancer. However, the reason remains unclear.

We also provided evidence that health care needs related to UTUC are significantly higher in this region than in the rest of the country, which is also true for bladder cancer.²

Based on the above facts, we believe that arsenic-exposed subjects in Antofagasta are an ideal target to develop strategies for early detection of urothelial carcinoma, especially considering all of the required resources for treatment and follow-up of these diseases.

Figure 1. Antofagasta region drinking water network

Written by: José Francisco López, MS, MD^1,2, Mario I. Fernández, MD³

Hospital de La Florida, Santiago, Chile
Oxford University Hospitals, Oxford, UK
Clínica Alemana, Santiago, Chile

References:

Ferreccio, Catterina, Allan H. Smith, Viviana Durán, Teresa Barlaro, Hugo Benítez, Rodrigo Valdés, Juan José Aguirre et al. "Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed Northern Chile." American journal of epidemiology 178, no. 5 (2013): 813-818.
Fernández, Mario I., J. Francisco López, Bruno Vivaldi, and Fernando Coz. "Long-term impact of arsenic in drinking water on bladder cancer health care and mortality rates 20 years after end of exposure." The Journal of urology 187, no. 3 (2012): 856-861.

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