Association of arsenic exposure with lung cancer incidence rates in the United States

Abstract

Background: Although strong exposure to arsenic has been shown to be carcinogenic, its contribution to lung cancer incidence in the United States is not well characterized. We sought to determine if the low-level exposures to arsenic seen in the U.S. are associated with lung cancer incidence after controlling for possible confounders, and to assess the interaction with smoking behavior.

Methodology: Measurements of arsenic stream sediment and soil concentration obtained from the USGS National Geochemical Survey were combined, respectively, with 2008 BRFSS estimates on smoking prevalence and 2000 U.S. Census county level income to determine the effects of these factors on lung cancer incidence, as estimated from respective state-wide cancer registries and the SEER database. Poisson regression was used to determine the association between each variable and age-adjusted county-level lung cancer incidence. ANOVA was used to assess interaction effects between covariates.

Principal findings: Sediment levels of arsenic were significantly associated with an increase in incident cases of lung cancer (P<0.0001). These effects persisted after controlling for smoking and income (P<0.0001). Across the U.S., exposure to arsenic may contribute to up to 5,297 lung cancer cases per year. There was also a significant interaction between arsenic exposure levels and smoking prevalence (P<0.05).

Conclusions/significance: Arsenic was significantly associated with lung cancer incidence rates in the U.S. after controlling for smoking and income, indicating that low-level exposure to arsenic is responsible for excess cancer cases in many parts of the U.S. Elevated county smoking prevalence strengthened the association between arsenic exposure and lung cancer incidence rate, an effect previously unseen on a population level.

Figure 1. of the extent of coverage and measured levels of arsenic by atomic absorption for the continental U.S.

The study area is delineated by a bolded outline. Original image is courtesy of the U.S. Geological Survey.

Figure 2. Scatter plot of fitted points showing the estimated association between arsenic and lung cancer incidence in the top 50% (triangles) and lower 50% (circles) smoking quantile.

The left figure shows the association without adjustment for median county income, and the right the same association after adjusting for median county income. The size of the dots is proportional to population. Shaded areas delineate the 95% confidence interval for the adjusted model, with the slope of each regression line and P-Value for the corresponding ANOVA listed in Table 3.

Figure 3. Bar plot showing the average level of exposures and outcomes for counties in West Virginia or Kentucky compared with the remaining 10 states in the original sample.

Arsenic exposure is listed as concentration in parts per million (ppm), income as thousands of dollars, incidence rate as annual lung cancer incidence per year per 100,000 persons, and smoking as the percentage of adults having self-reported lifetime smoking. Asterisks (*) indicate statistical significance at P<0.05 in the unpaired t-test.

Figure 4. Histogram of the residuals for counties in West Virginia and Kentucky when the model developed on the full 12-state sample was applied (left), with a plot of the measured values for both incidence rate and Arsenic exposure (right).

The solid line represents the estimated association between arsenic and lung cancer incidence across the entire sample, with the grey shading representing the 95% confidence interval for the estimate.