Metabolic syndrome and thyroid Cancer: risk, prognosis, and mechanism

Abstract

The increasing incidence of thyroid cancer (TC) cannot be fully explained by overdiagnosis. Metabolic syndrome (Met S) is highly prevalent due to the modern lifestyle, which can lead to the development of tumors. This review expounds on the relationship between Met S and TC risk, prognosis and its possible biological mechanism. Met S and its components were associated with an increased risk and aggressiveness of TC, and there were gender differences in most studies. Abnormal metabolism places the body in a state of chronic inflammation for a long time, and thyroid-stimulating hormones may initiate tumorigenesis. Insulin resistance has a central role assisted by adipokines, angiotensin II, and estrogen. Together, these factors contribute to the progression of TC. Therefore, direct predictors of metabolic disorders (e.g., central obesity, insulin resistance and apolipoprotein levels) are expected to become new markers for diagnosis and prognosis. cAMP, insulin-like growth factor axis, angiotensin II, and AMPK-related signaling pathways could provide new targets for TC treatment.

The Tumor Microenvironment and the Estrogen Loop in Thyroid Cancer

“…All of the above-mentioned factors participate in the establishment of a low-grade, chronic inflammatory state, which is typical of metabolic syndrome, and which, in turn, lays the foundation for the development of a plethora of pathologic states-including cardiovascular, autoimmune, metabolic and, notably, oncologic diseases. As previously described, activated AKT/mTOR/PI3K and ERK /MAPK signaling fosters angiogenesis, cell proliferation, transformation and invasion, overall, promoting carcinogenesis [87].…”

“…In this context, several studies have assessed the potential impact of metabolic syndrome components on TC incidence and outcomes: interestingly, obesity, hyperglycemia (especially in female patients), hypertension and dyslipidemia do appear to contribute to TC development and progression; conversely, studies addressing the effects on TC prognosis have yielded more controversial results, owing to the lack of large-scale, long-term, prospective analyses [87].…”

Obesity and thyroid cancer risk

“…The relationship between thyroid cancer and obesity may also be mediated by other markers of adverse metabolic health [43]. A large meta-analysis found a significant association between type two diabetes mellitus and thyroid cancer, after adjustment for BMI [44], and a recent cohort study found a significant association between metabolic syndrome and risk of thyroid cancer (RR = 1.19, 95%CI 1.14–1.24 in men; RR = 1.16, 95%CI 1.13–1.19 in women) [45 ▪ ].…”

“…A large prospective study demonstrated that doubling of IGF-1 was associated with an increased thyroid cancer risk (RR = 1.48, 95%CI 1.06–2.08) [58]. Thyroid tumors also express insulin receptors and therefore activation may drive oncogenesis [43,47,50]. Likewise, obesity increases estrogen levels via aromatase-mediated conversion of androgens in adipose tissue.…”

The Lactate Receptor GPR81 is a Mechanism of Leukemia-Associated Macrophage Polarization in the Bone Marrow Microenvironment

“…These pathways primarily coordinate the axis between oxidative phosphorylation and glycolysis, and shifts in metabolism can influence cell phenotype, for example, the activation phenotype of macrophages 50 . Lactate-GPR81 signaling was found to reprogram glucometabolism in breast cancer cells and directly contribute to the immune landscape in the TME 51 . Downstream of GPR81 activation in cancer cells, pathways are upregulated for growth and survival, DNA repair proteins, chemoresistance (ex.…”