## 4 Selenium in Thyroid Bland
### Selenium and Thyroid Cancer
The expression of antioxidant proteins increases in many types of cancer and decreases in others [99]. Indeed, tumor cells present major differences in their selenoprotein expression pattern such as the GPx gene [92]. In colorectal cancer, 15 selenoprotein genes were analyzed in two cohorts. Both selenoproteins TRx3 and GPx2 were upregulated in adenoma and carcinoma, while SePP and selenoprotein S were down regulated [113]. The increased gene expression of GPx2 and TRx3 can be explained by the fact that both are target genes for Wnt signaling. This signaling pathway is activated in most colorectal cancer tissues [114]. However, there are not many studies regarding the overall changes in selenoprotein genes in thyroid cancer. Selenoproteins GPx1 and TRx1 in thyroid cancer tissue are lower in patients versus controls, while DIO3 mRNA levels and activity were increased in PTC [111; 115]. This increase in DIO3 mRNA levels was correlated with distant metastasis or lymph nodes. Thus, it appears that some selenoproteins fight the growth of tumor cells, while others support it, which underlines the fact that the carcinogenesis mechanisms linked to the Se status are far from being elucidated [115]. Experiments have suggested that selenoproteins can act to modulate the susceptibility of the malignancy by acting on tumor suppressor gene pathways. It has been observed in breast and prostate cancer that selenoproteins carry on, for example, control in the checkpoint kinase-2 (CHEK2) gene, a suppressor tumor gene which is involved in the signal transduction in cellular response to DNA damage who is associated with thyroid malignancy [116]. Different mutations in the tumor suppressor gene CHEK2, such as 1100 delC, IVS2 1 1G \(>\) A, del5395 and I157T, are associated with multi-organ cancers including breast and papillary thyroid cancer [117]. In addition, Se could act as an anti-mutagenic agent with toxicity against cancer cells [118]. Se acts by inducing cell death by production of superoxide radicals thus triggering the mitochondrial pathway of apoptosis, while sparing healthy cells [118]. It is clear that Se has anticarcinogenic properties, linked to its valence states. Selenite has the capacity to intervene in redox reactions, while selenate is completely devoid of this ability [119]. It is reported in a review by [PERSON] et al. that only selenite ions react with the -SH groups of proteins and prevent the formation of protein polymers rich in disulfides [119]. Indeed, a barrier made up of blood proteins with fibrin properties, protects the membranes of cancer cells from recognition by the immune system. Sodium selenite inhibits the protein disulfide exchange on the surface of cancer cell membranes and thus makes the tumor sensitive to the destructive activity of phagocytic cells [119]. Selenium supplementation has positive results in autoimmune thyroid disease and may improve thyroid cancer outcome, however the results are not conclusive in the majority of cases [95]. The question that remains is whether a deficiency in this micronutrient is a consequence of thyroid cancer or a risk factor. The example of hypoxia, which can influence selenoproteins biosynthesis, the expression of SePP is reduced noting a decrease in the distribution of Se by hepatocytes causing a general decline in selenoproteins expression [120; 121; 122]. To conclude, several studies have highlighted a Se deficiency in thyroid cancer patients. However, in the lack of evidence to this relationship, many studies are needed to confirm and to explain this hypothesis.