Tommaso Filippini1, Carlotta Malagoli1, Lauren A Wise2, Marcella Malavolti1, Giovanni Pellacani3, Marco Vinceti4. 1. Environmental, Genetic and Nutritional Epidemiology Research Center, Department of Biomedical, Metabolic and Neural Sciences - Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy. 2. Department of Epidemiology, Boston University School of Public Health, Boston, USA. 3. Department of Dermatology, University of Modena and Reggio Emilia, Italy. 4. Environmental, Genetic and Nutritional Epidemiology Research Center, Department of Biomedical, Metabolic and Neural Sciences - Section of Public Health, University of Modena and Reggio Emilia, Modena, Italy; Department of Epidemiology, Boston University School of Public Health, Boston, USA. Electronic address: marco.vinceti@unimore.it.
Abstract
INTRODUCTION: Exposure to the heavy metal cadmium has been associated with many adverse health effects, such as atherosclerosis, diabetes, and cancer, possibly melanoma. In non-occupationally exposed individuals, food intake is a major source of cadmium exposure, after smoking. We aimed to assess the risk of melanoma in relation to dietary cadmium intake. METHODS: Using a population-based case-control study design, we recruited 380 incident cases of newly-diagnosed cutaneous melanoma and 719 matched controls in the Emilia-Romagna Region, Northern Italy in the years 2005-2006. We evaluated dietary intake using a semi-quantitative food frequency questionnaire. We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for melanoma according to quintiles of dietary cadmium intake, adjusting for several potential confounders, and we modeled the association non-parametrically, using restricted cubic splines. RESULTS: Median energy-adjusted intake of cadmium was 6.11 μg/day (interquartile range 5.38-6.91) among cases and 5.97 μg/day (5.15-6.79) among controls. For each 1 μg/day-increase in cadmium intake, the OR for melanoma was 1.11 (95% CI 1.00-1.24). Melanoma risk generally increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) for the second through fifth quintiles, compared with the lowest quintile. Sex-stratified analysis showed ORs per 1 μg/day-increase in cadmium intake of 1.10 (95% CI 0.93-1-29) among men and 1.15 (95% CI 0.99-1.33) among women. Using spline regression analysis, we observed a generally linear increase in melanoma risk up to 6 μg/day of cadmium intake, after which the risk appeared to plateau. CONCLUSIONS: We observed a positive non-linear association between dietary cadmium intake and risk of cutaneous melanoma in a Northern Italy population. However, further studies are needed to elucidate this association, due to concerns about exposure misclassification, unmeasured confounding, and the limited and conflicting evidence from epidemiological findings.
INTRODUCTION: Exposure to the heavy metalcadmium has been associated with many adverse health effects, such as atherosclerosis, diabetes, and cancer, possibly melanoma. In non-occupationally exposed individuals, food intake is a major source of cadmium exposure, after smoking. We aimed to assess the risk of melanoma in relation to dietary cadmium intake. METHODS: Using a population-based case-control study design, we recruited 380 incident cases of newly-diagnosed cutaneous melanoma and 719 matched controls in the Emilia-Romagna Region, Northern Italy in the years 2005-2006. We evaluated dietary intake using a semi-quantitative food frequency questionnaire. We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs) for melanoma according to quintiles of dietary cadmium intake, adjusting for several potential confounders, and we modeled the association non-parametrically, using restricted cubic splines. RESULTS: Median energy-adjusted intake of cadmium was 6.11 μg/day (interquartile range 5.38-6.91) among cases and 5.97 μg/day (5.15-6.79) among controls. For each 1 μg/day-increase in cadmium intake, the OR for melanoma was 1.11 (95% CI 1.00-1.24). Melanoma risk generally increased with increasing quintile of cadmium exposure, with ORs of 1.55 (95% CI 0.99-2.42), 1.54 (95% CI 0.99-2-40), 1.75 (95% CI 1.12-2.75), and 1.65 (95% CI 1.05-2.61) for the second through fifth quintiles, compared with the lowest quintile. Sex-stratified analysis showed ORs per 1 μg/day-increase in cadmium intake of 1.10 (95% CI 0.93-1-29) among men and 1.15 (95% CI 0.99-1.33) among women. Using spline regression analysis, we observed a generally linear increase in melanoma risk up to 6 μg/day of cadmium intake, after which the risk appeared to plateau. CONCLUSIONS: We observed a positive non-linear association between dietary cadmium intake and risk of cutaneous melanoma in a Northern Italy population. However, further studies are needed to elucidate this association, due to concerns about exposure misclassification, unmeasured confounding, and the limited and conflicting evidence from epidemiological findings.