Relación entre la exposición a mezclas de metales pesados y semimetales y el riesgo de desarrollar cáncer en la cohorte EPIC-España

Abstract

Introduction. Available scientific literature to date suggests that environmental factors are involved in cancer development. While some heavy metals and metalloids (MPS) are carcinogens, their association with cancer depends on the element analyzed. Most studies focus on the individual effect of MPS. Therefore, the aim of this doctoral thesis was to estimate the association between exposure to MPS and the risk of developing cancer in the EPIC (European Prospective Investigation into Cancer and Nutrition)-Spain cohort, considering the joint effect of the mixture. Materials and methods. We conducted a case-control study within the EPIC-Spain cohort. The analytic sample comprised 578 women, including 286 incident breast cancer cases and 292 cancer-free controls. Plasma concentrations of 16 MPS were quantified at recruitment, while cancer diagnosis was retrieved from Population-Based Cancer Registries (RCBP). Mixed-effect multivariable logistic regression models were applied to explore the effect of individual MPS. Quantile-based g-computation (QgC) models were applied to identify the main mixture components and to estimate the joint effect of the mixture of MPS. Results. The geometric means were higher for Cu (845.6 ng/ml) and Zn (604.8 ng/ml). Cases had significantly higher concentrations (p=0.010) and significantly lower Zn concentrations (p<0.001). Cu (+0.42) and Mn (+0.13) showed the highest positive weights, whereas Zn (–0.61) and W (–0.16) showed the highest negative weights. The joint effect of the mixture of MPS was estimated at an OR=4.51 (95% CI=2.32–8.79), suggesting a dose-response relationship. No evidence of non-linearity or nonadditivity was found. The mixture effect was associated with essential (p<0.001) but not with non-essential elements. Conclusions. An unfavorable exposure profile, primarily characterized by high Cu and low Zn levels, could lead to a significant increase in the risk of developing female breast cancer in the EPIC-Spain cohort, independently of other known risk factors. Further studies assessing multiple biological matrices and a variety of exposure scenarios are warranted to corroborate our findings.