Dietary cadmium intake and risk of cutaneous melanoma: a population-based case-control study in Northern Italy

BACKGROUND AND AIM. Cadmium is a toxic heavy metal for humans, and its environmental exposure has been linked to many adverse health effects, including cancer, atherosclerosis and diabetes. In particular, recent findings suggest that cadmium may increase risk of cutaneous melanoma, possibly through the promotion of the malignant transformation of melanoma cells through aberrant DNA methylation and by inducing gene expression dysregulation. Since in non-occupational exposed and non-smoking subjects dietary exposure is the major source of cadmium exposure, we aimed to assess melanoma risk in relation to dietary cadmium intake. METHODS. We recruited 380 newly-diagnosed incident cases of cutaneous melanoma and 719 sex- and age-matched population controls in four North Italian provinces (Parma, Reggio Emilia, Modena, and Bologna) of Emilia-Romagna Region. We estimated their dietary habits using a semi-quantitative food frequency questionnaire and we evaluated melanoma risk by computing the odds ratio (OR) and its 95% confidence interval (CI) according to quintile distribution of cadmium intake. We used a conditional logistic regression model to compute ORs, matching by sex, age and province of residence, and adjusting also for phototype, non-alcoholic energy intake, body mass index, and Italian Mediterranean Diet Index. Also a spline regression model was used in order to evaluated possible dose-response relation. RESULTS: Median cadmium intake was 5.81 µg/day (interquartile range 4.46-7.59) in cases, and 5.63 µg/day (4.46-7.34) in controls. OR of melanoma associated with 1-unit increase in cadmium intake was 1.11 (95% CI 1.00-1.24). Melanoma risk 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) from second to highest quintile compared to lowest quintile. Sex-stratified analysis showed substantially comparable results and a generally higher risk in women, with continuous ORs of 1.10 (95% CI 0.93-1-29), and 1.15 (95% CI 0.99-1.33) in men and women, respectively. Spline regression analysis showed a non-linear risk increase, with possible plateau at 5-6 µg/day of cadmium intake. Slightly higher risk estimates in women and older subjects were detected. CONCLUSIONS: Our results seem to point out a positive association between dietary cadmium exposure and melanoma risk in the study population. Such association started to occur at a level of exposure lower than the tolerable intake established for food safety by international authorities.