Estrogen and its role in thyroid cancer

Abstract

Proliferative thyroid diseases are more prevalent in females than in males. Upon the onset of puberty, the incidence of thyroid cancer increases in females only and declines again after menopause. Estrogen is a potent growth factor both for benign and malignant thyroid cells that may explain the sex difference in the prevalence of thyroid nodules and thyroid cancer. It exerts its growth-promoting effect through a classical genomic and a non-genomic pathway, mediated via a membrane-bound estrogen receptor. This receptor is linked to the tyrosine kinase signaling pathways MAPK and PI3K. In papillary thyroid carcinomas, these pathways may be activated either by a chromosomal rearrangement of the tyrosine receptor kinase TRKA, by RET/PTC genes, or by a BRAF mutation and, in addition, in females they may be stimulated by high levels of estrogen. Furthermore, estrogen is involved in the regulation of angiogenesis and metastasis that are critical for the outcome of thyroid cancer. In contrast to other carcinomas, however, detailed knowledge on this regulation is still missing for thyroid cancer.

Thyroid Cancers: Considerations, Classifications, and Managements

“…Estrogen is also another potential risk factor for papillary thyroid carcinoma, which justiies the sex diference for thyroid nodules and carcinoma [22]. Hepatitis C infection has been mentioned as a potential risk factor for thyroid cancer; however, more studies are needed to conirm this association [23].…”

“…Based on a meta-analysis, each 5-unit increase in body mass index (BMI), 5 kg increase in weight, 5 cm increase in waist or hip circumference, and 0.1 unit increase in waistto-hip ratio were associated with 30, 5, 5, and 14% greater risks of thyroid cancer, respectively [21]. Estrogen is also another potential risk factor for papillary thyroid carcinoma, which justiies the sex diference for thyroid nodules and carcinoma [22]. Hepatitis C infection has been mentioned as a potential risk factor for thyroid cancer; however, more studies are needed to conirm this association [23].…”

Factores Asociados a la Recurrencia Tumoral en Mujeres con Carcinoma Diferenciado de Tiroides

“…Esta diferencia de sexo ha sido relacionada hipotéticamente a las fluctuaciones de las hormonas sexuales que se producen en determinadas etapas de la vida de la mujer (ciclo menstrual, embarazo y pre o perimenopausia) [20]. Sin embargo, la evidencia de esta relación aún no es concluyente [19].El papel de las hormonas sexuales femeninas en la patogénesis y progresión del cáncer de tiroides aún existe un vacío sustancial en la comprensión del significado que tienen los estrógenos y sus receptores α y β [21]. En gestantes con microcarcinoma papilar, por ejemplo, se ha observado la progresión del carcinoma [22,23], y se señala la posible mayor persistencia y recurrencia del mismo.…”

Thyroid tumors: are we unveiling the puzzle?

“…In fact, in another review of this issue, Derwahl & Nicula (2014) explore the role of estrogen in thyroid tumors, demonstrating that, besides being a potent growth factor for both benign and malignant thyroid cells, estrogen exerts its growth-promoting effect via a membrane-bound link to the tyrosine kinase signaling pathways MAPK and PI3K. In addition, the fact that estrogen is involved in the regulation of angiogenesis and metastasis may explain the differences observed in the clinical evolution between genders (Jonklaas et al 2012).…”

“…In addition, the fact that estrogen is involved in the regulation of angiogenesis and metastasis may explain the differences observed in the clinical evolution between genders (Jonklaas et al 2012). It is important to notice that estrogen may also be an important stimulator of stem and progenitor cells (Derwahl & Nicula 2014). These cells may be responsible for a subset of thyroid tumors, which are resistant to chemo and radiation therapies.…”