Cadmium Exposure and Cancer Mortality in a Prospective Cohort: The Strong Heart Study

Abstract

Background: Cadmium (Cd) is a toxic metal classified as a human carcinogen by the International Agency for Research on Cancer.Objective: We evaluated the association of long-term Cd exposure, as measured in urine, with cancer mortality in American Indians from Arizona, Oklahoma, and North and South Dakota who participated in the Strong Heart Study during 1989–1991.Methods: The Strong Heart Study was a prospective cohort study of 3,792 men and women 45–74 years of age who were followed for up to 20 years. Baseline urinary Cd (U-Cd) was measured using inductively coupled plasma mass spectrometry. We assessed cancer events by annual mortality surveillance.Results: The median (interquintile range) U-Cd concentration was 0.93 (0.55, 1.63) μg/g creatinine. After adjusting for sex, age, smoking status, cigarette pack-years, and body mass index, the adjusted hazard ratios (HRs) comparing the 80th versus the 20th percentiles of U-Cd were 1.30 (95% CI: 1.09, 1.55) for total cancer, 2.27 (95% CI: 1.58, 3.27) for lung cancer, and 2.40 (95% CI: 1.39, 4.17) for pancreatic cancer mortality. For all smoking-related cancers combined, the corresponding HR was 1.56 (95% CI: 1.24, 1.96). Cd was not significantly associated with liver, esophagus and stomach, colon and rectum, breast, prostate, kidney, or lymphatic and hematopoietic cancer mortality. On the basis of mediation analysis, we estimated that the percentage of lung cancer deaths due to tobacco smoking that could be attributed to Cd exposure was 9.0% (95% CI: 2.8, 21.8).Conclusions: Low-to-moderate Cd exposure was prospectively associated with total cancer mortality and with mortality from cancers of the lung and pancreas. The implementation of population-based preventive measures to decrease Cd exposure could contribute to reducing the burden of cancer.Citation: García-Esquinas E, Pollan M, Tellez-Plaza M, Francesconi KA, Goessler W, Guallar E, Umans JG, Yeh J, Best LG, Navas-Acien A. 2014. Cadmium exposure and cancer mortality in a prospective cohort: the Strong Heart Study. Environ Health Perspect 122:363–370; http://dx.doi.org/10.1289/ehp.1306587

Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence

“…Of the reports based on the same population, those with the longest follow-up or no restrictions to specific inclusion, e.g., age groups, were included. Therefore, our meta-analysis consisted of two US populations, i.e., the NHANES III [10] and the Strong Heart Study [12], and the follow-up of the Belgian Cadmibel Study [9] together comprising 20,459 participants. The three study populations had a similar sex distribution (range 41-48 % men), and their average urinary cadmium concentration ranged from 0.25 to 0.93 lg/g creatinine.…”

“…In all reports, the results were adjusted for age and smoking and either adjusted or stratified for sex. Two studies [10,12] reported stratified analysis for smokers and non-smokers in a subanalysis and were used in a sensitivity analysis to show the robustness of the available data.…”

“…[12] and Adams et al [10] conducted a subanalysis in which smokers at baseline were excluded or only never-smokers were included, respectively. The sensitivity analysis of the two subgroups resulted for a doubling of urinary cadmium in a pooled relative risk of 1.07 (95 % CI 0.96-1.20; p = 0.21) for total cancer and 1.58 (95 % CI 1.08-2.31; p = 0.018) for lung cancer.…”

“…First, the median urinary cadmium levels in the Japanese studies were very high, ranging from 4.6 to 12.1 lg/g creatinine [28][29][30][31], which might explain the increased mortality from nephritis and nephrosis [32]. For comparison, the median urinary cadmium at baseline was 0.82 lg/ g creatinine in the Cadmibel Study [9] and 0.25-0.34 lg/g creatinine in the NHANESIII survey [10,14], while in the Strong Heart Study [12] (American Indian communities), the urinary cadmium was higher and averaged 0.93 lg/g creatinine. Furthermore, the Japanese studies [28][29][30] provided standardized mortality rates instead of hazard rates or relative risks or did not adjust for smoking and therefore were not included in the current meta-analysis to prevent heterogeneity.…”

“…In 2006, we were the first to provide prospective evidence for an association between lung cancer and environmental cadmium exposure [9]. In the last 5 years, five US studies [10][11][12][13][14] further reported on the association between cancer and urinary cadmium. Here, we investigated the strength and consistency of the putative role of low-dose environmental cadmium in association with increased total cancer and lung cancer.…”