Reactive oxygen species (ROS) are the most critical class of free radicals or reactive metabolites produced by all living organisms. ROS regulate several cellular functions through redox-dependent mechanisms, including proliferation, differentiation, hormone synthesis, and stress defense response. However, ROS overproduction or lack of appropriate detoxification is harmful to cells and can be linked to the development of several diseases, such as cancer. Oxidative damage in cellular components, especially in DNA, can promote the malignant transformation that has already been described in thyroid tissue. In thyrocyte physiology, NADPH oxidase enzymes produce large amounts of ROS that are necessary for hormone biosynthesis and might contribute to the high spontaneous mutation rate found in this tissue. Thyroid cancer is the most common endocrine malignancy, and its incidence is significantly higher in women than in men. Several lines of evidence suggest the sex hormone estrogen as a risk factor for thyroid cancer development. Estrogen in turn, besides being a potent growth factor for both normal and tumor thyroid cells, regulates different mechanisms of ROS generation. Our group demonstrated that the thyroid gland of adult female rats exhibits higher hydrogen peroxide (H₂O₂) production and lower enzymatic antioxidant defense in comparison with male glands. In this review, we discuss the possible involvement of thyroid redox homeostasis and estrogen in the development of thyroid carcinogenesis.

NOX/DUOX enzymes are transmembrane proteins that carry electrons through biological membranes generating reactive oxygen species. The NOX family is composed of seven members, which are NOX1 to NOX5 and DUOX1 and 2. DUOX enzymes were initially called thyroid oxidases, based on their high expression level in the thyroid tissue. However, DUOX expression has been documented in several extrathyroid tissues, mostly at the apical membrane of the salivary glands, the airways, and the intestinal tract, revealing additional cellular functions associated with DUOX-related H2O2 generation. In this review, we will briefly summarize the current knowledge regarding DUOX structure and physiological functions, as well as their possible role in cancer biology.

NADPH oxidase enzymes (NOX) are involved in all stages of carcinogenesis, but their expression levels and prognostic value in breast cancer (BC) remain unclear. Thus, we aimed to assess the expression and prognostic value of NOX enzymes in BC samples using online databases. For this, mRNA expression from 290 normal breast tissue samples and 1904 BC samples obtained from studies on cBioPortal, Kaplan–Meier Plotter, and The Human Protein Atlas were analyzed. We found higher levels of NOX2, NOX4, and Dual oxidase 1 (DUOX1) in normal breast tissue. NOX1, NOX2, and NOX4 exhibited higher expression in BC, except for the basal subtype, where NOX4 expression was lower. DUOX1 mRNA levels were lower in all BC subtypes. NOX2, NOX4, and NOX5 mRNA levels increased with tumor progression stages, while NOX1 and DUOX1 expression decreased in more advanced stages. Moreover, patients with low expression of NOX1, NOX4, and DUOX1 had lower survival rates than those with high expression of these enzymes. In conclusion, our data suggest an overexpression of NOX enzymes in breast cancer, with certain isoforms showing a positive correlation with tumor progression.