Endocrine-disrupting chemicals and endocrine neoplasia: A forty-year systematic review

Introduction: Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumouri-genic chemicals. Studies show that even EDCs which were long abolished are still contributing to the increasing incidence of neoplasia.Aim: To investigate the association between human exposure to EDCs and the risk of endocrine-related tumours: breast, prostate, thyroid, uterus, testis, and ovary.Methods: A systematic review using PubMed, Scopus, and Embase was conducted, searching for original obser-vational studies published between 1980 and 2020, approaching EDCs exposure and endocrine tumourigenic risk in humans. We comprised neoplasia of six endocrine organs. We included all the studies on EDCs reporting tumour odds ratio, risk ratio, or hazard ratio. Study levels of confidence and risk of bias were accessed applying accredited guidelines. Human-made accidents and natural EDCs were not considered in the present study.Results: Our search returned 3271 papers. After duplicate removal and screening, only 237 papers were included (corresponding to 268 records). EDCs were grouped from the most frequently (pesticides) to the least frequently studied (salts). The most tumourigenic EDC groups were phthalates (63%), heavy metals (54%), particulate matter (47%), and pesticides (46%). Pesticides group comprised the highest number of retrieved studies (n = 133). Increased neoplasia risk was found in 43-67% of the studies, with a lower value for ovary (43%) and a higher value for thyroid (67%).Conclusions: The innovative nature of our review comes from including human studies of six endocrine-related neoplasia aiming to understand the contribution of specific EDCs groups to each organ's tumourigenesis. Thy-roid was the organ presenting the highest cancer risk after EDC exposure which may explain the increasing thyroid cancer incidence. However, detailed and controlled works reporting the effects of EDCs are scarce, probably justifying conflicting results. Multinational and multicentric human studies with biochemical analysis are needed to achieve stronger and concordant evidence.