Heavy Metals in the Environment and Thyroid Cancer

SIMPLE SUMMARY: Epidemiological observations indicate that the incidence of thyroid cancer is increased in volcanic areas. Indeed, in the volcanic area of Sicily, where residents are biocontaminated by volcano-originated, low-level, multi-elemental metal pollution, the thyroid cancer incidence is double that in non-volcanic areas. The aim of this review is to summarize the evidence suggesting that chronic exposure to heavy metals, even at slightly increased environmental concentrations that cause no harm to mature thyrocytes, may alter the biology of stem/precursor thyroid cells, leading to a predisposition to malignant transformation. Both in vitro and in vivo experiments support this possibility; this phenomenon involves a variety of molecular mechanisms depending on the metal and the target cell involved. The role of the increased and generalized metal pollution in our ecosystem, paralleling the worldwide increase in thyroid cancer in recent decades, requires more attention and further studies. ABSTRACT: In recent decades, the incidence of thyroid cancer has increased more than most other cancers, paralleling the generalized worldwide increase in metal pollution. This review provides an overview of the evidence supporting a possible causative link between the increase in heavy metals in the environment and thyroid cancer. The major novelty is that human thyroid stem/progenitor cells (thyrospheres) chronically exposed to different metals at slightly increased environmentally relevant concentrations show a biphasic increase in proliferation typical of hormesis. The molecular mechanisms include, for all metals investigated, the activation of the extracellular signal-regulated kinase (ERK1/2) pathway. A metal mixture, at the same concentration of individual metals, was more effective. Under the same conditions, mature thyrocytes were unaffected. Preliminary data with tungsten indicate that, after chronic exposure, additional abnormalities may occur and persist in thyrocytes derived from exposed thyrospheres, leading to a progeny population of transformation-prone thyroid cells. In a rat model predisposed to develop thyroid cancer, long-term exposure to low levels of metals accelerated and worsened histological signs of malignancy in the thyroid. These studies provide new insight on metal toxicity and carcinogenicity occurring in thyroid cells at a low stage of differentiation when chronically exposed to metal concentrations that are slightly increased, albeit still in the “normal” range.