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Factors Predisposing to Thyroid cancer

المؤلف:  Wass, J. A. H., Arlt, W., & Semple, R. K. (Eds.).

المصدر:  Oxford Textbook of Endocrinology and Diabetes

الجزء والصفحة:  3rd edition , p600-601

2026-05-21

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 Radiation exposure of the thyroid gland is the most established PTC risk factor. The thyroid is particularly vulnerable to ionizing radiation, with the paediatric population being the most sensitive. Similar to many organs of the body, ionizing radiation may lead to thyroid DNA damage. Depending on the modality and severity of irradiation, it may cause cell death or, if less severe, it may result in specific genetic abnormalities. Accordingly, radiation exposure has been associated with increased formation of oncogenic rearrangements in TC.

Iodine intake demonstrates a well- known impact on the incidence and prevalence of thyroid disease and TC. It is believed that iodine prophylaxis changed the epidemiology of DTC. However, there is still a lack of evidence- based data supporting this hypothesis. Iodine deficiency is associated with an increased FTC risk, whereas PTC is more prevalent in regions with sufficient iodine supplementation. Also, the question about the potential role of iodine intake in the increased TC incidence and mechanisms linking the iodine intake and TC remains open. Chronic thyroid- stimulating hormone (TSH) stimulation and BRAF mutations are among considered pathways.

Some studies demonstrated an increased TC risk in obese individuals, probably related to insulin resistance.

Information regarding food factors is as yet not conclusive. Some analyses demonstrated decreased TC risk in individuals on fruit, raw, or mixed vegetable diet. Conversely, cruciferous vegetables may increase TC risk. The data concerning the impact of meat or dairy consumption are also inconclusive.

One of the highest TC incidences worldwide is noticed in volcanic regions. Active volcanoes produce numerous toxic compounds that might contaminate cultivated fields and affect the animal and food chain that could be involved in thyroid cancerogenesis.

Xenobiotics— exogenous compounds and chemicals— may competitively inhibit sodium/ iodide symporter, thyroid peroxidase, deiodinase, binding of thyroid hormones to transport proteins, or to thyroid hormone receptors or induce hepatic metabolism of thy roid hormones leading to decreased serum thyroxine concentration and increased TSH level. The question of whether xenobiotics pro mote or not TC has not been addressed yet.

There is a little evidence of a potential association of herpes viruses and DTC, and of a possible role of Epstein– Barr virus in thy roid tumorigenesis.

Another important issue is the autoimmune Hashimoto’s thyroiditis (HT). Elevated TSH levels, stimulating follicular cells proliferation and promoting TC development, secretion of proinflammatory cytokines, and oxidative stress are considered as plausible mechanisms linking TC risk and HT. Interestingly, while studies using fine- needle aspiration biopsy (FNAB) specimens did not demonstrate an increased PTC risk in HT, surgical series with histopathological assessment found the coexistence of PTC and HT. However, biased results should be considered.

As TC is more frequent in women, oestrogens are considered a possible risk factor. Oestrogens and cognate receptors are important factors influencing proliferation, migration, and invasion of TC cells in vitro. A comparison between 40 TC women and 40 age- matched controls showed that oestrogen metabolism was unbalanced in TC and suggested a possible role of oestrogen- DNA adducts in TC initiation. A significantly higher TC risk was observed in postmenopausal women with hysterectomy comparing to women without hysterectomy, regardless of the ovarian status. Interestingly, when a hysterectomy group was considered alone, hormone therapy was related to a lower TC risk. According to the recently published review, there was a weak association between DTC risk and menstrual or menopausal factors, oral contraceptives, and hormone replacement therapy. Regarding pregnancy, the question of a possible association between the parity and DTC risk remains unanswered. Some reports suggested a possible impact of pregnancy- related factors on DTC progression and short- term outcome in comparison with non- pregnant controls. On the other hand, there is probably no impact of pregnancy on DTC- related death or overall survival. In conclusion, further studies are necessary to provide more direct evidence of the oestrogenic impact on thyroid tumorigenesis.

Medullary thyroid cancer (MTC) in up to 25% of cases is related to a genetic predisposition in the frame of MEN 2A and MEN 2B syndromes caused by germline mutations of the RET gene. Non- medullary TC may also develop in some cases in the frame of complex genetic syndromes, including familial adenomatous polyposis, Cowden syndrome, or Carney’s complex. Recently, a familial DICER1 tumour syndrome caused by germline inactivating DICER1 mutations has been defined. DICER1 is involved in microRNAs maturation by cleaving ribonucleic acid (RNA) pre cursors into siRNA and miRNA. Unfortunately, besides these particular conditions, genetic heterogeneity makes it difficult to identify the TC cause in most individual families.