Rising thyroid cancer incidence in the world might be related to insulin resistance
Introduction
The metabolic syndrome (MetS) is associated with cardiovascular risk factors. Insulin resistance (IR) is considered as the central pathological link among these risk factors [1]. Beside increased cardiovascular disease risk, MetS has also been associated with several common adult cancers. Although exact molecular mechanisms and the pathophysiology responsible for increased risk are not fully understood, a part of this carcinogenic effect could be attributed to IR. Increased insulin levels, which is a consequence of IR, decrease the production of insulin-like growth factor-1 (IGF-1) binding proteins and hence increase levels of free IGF-1. The IGFs are produced by many tissues and their receptors are expressed in most cancer cells, where it displays potent antiapoptotic, cell-survival, and transforming activities [2]. In this context, IGF and its receptor expression is a fundamental prerequisite for the acquisition of a malignant phenotype.
In the USA, the prevalence of obesity, hence IR, has increased from 15.3% in 1995 to 23.9% in 2005 [3]. In a similar trend, although the mortality rate has remained stable, the incidence of thyroid cancer is rising. Although this recent rise in thyroid cancer is likely related to improved imaging modalities, altered histopathologic criteria for diagnosis of thyroid cancer, and nuclear exposure, it should be questioned whether there are other modifiable risk factors contributing to this increased risk [4], [5], [6].
The reported clinical data about the association of MetS and its related components, especially IR, with the thyroid gland morphology are scarce. In previous reports by Rezzonico et al. and our group, patients with IR have larger thyroid volumes and higher risk for formation of thyroid nodules [7], [8]. Both studies concluded that the higher circulating levels of insulin cause increased thyroid proliferation and thyroid nodules. In a small cross-sectional study by Rezzonico et al., it was also shown that increased prevalence of IR is present in patients with differentiated thyroid carcinoma [9]. Previous studies support the concept that insulin along with thyroid stimulating hormone (TSH) functions as a growth factor and stimulates thyroid cell proliferation. This effect, at least in part, is mediated via IGF-1 dependent mechanisms; therefore, IGF-1 might be involved in the pathogenesis of thyroid morphological abnormalities and cancer development [10], [11], [12], [13].
Section snippets
Hypothesis
Recent reports put a significant association of IR with increased thyroid nodule prevalence. These studies concluded that IR would be an important risk factor for developing differentiated thyroid cancer, as it is well known with some other nonthyroid carcinomas [7], [8], [9]. Increased IGF-I and IGF-I receptor immunoreactivity in human thyroid carcinomas with an associated up-regulation of IGF-I mRNA were previously reported [14]. It has also been shown that insulin receptors are overexpressed
Discussion
Carcinogenesis is a dynamic interplay between stimulatory and inhibitory factors involving in cell growth and differentiation. Cancer growth in this manner appears to involve hormonal, paracrine and/or autocrine regulatory mechanisms [16]. TSH is a major hormone that plays an important role in regulating the growth and differentiation of thyroid cells [17]. Some humoral or hormonal mediators from adipose tissue stimulate the hypothalamus–pituitary–thyroid axis to increase TSH secretion [18].
Conflict of interest statement
None declared.
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