Dietary cadmium intake and risk of cutaneous melanoma: An Italian population-based case-control study

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.