Estrogens and Stem Cells in Thyroid Cancer

Zane, Mariangela; Catalano, Veronica; Scavo, Emanuela; Bonanno, M; Pelizzo, Maria Rosa; Todaro, Matilde; Stassi, Giorgio

doi:10.3389/fendo.2014.00124

Cited by 18 publications

(27 citation statements)

References 99 publications

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“…However, the incidence of thyroid cancer was found to be increased for infertile women who have taken estrogen. A previous study has shown that estrogens increase the expression of thyroid‐stimulating hormone, which increases the mitotic activity of the follicular cells in the thyroid gland and increases the development of thyroid cancer . Thyroid cancer is the second most common cancer diagnosed in pregnant women, which could be related to the increased use of human chorionic gonadotropin and estrogen during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…Estrogen may be related to the indirect effect through increasing thyroid hormone–binding globulin, and the direct effect through the estrogen receptors α and β. Estrogen metabolism is reported to be unbalanced in women with thyroid cancer . Estrogens promote thyroid cell proliferation and affect the stem cell propagation in the thyroid gland . A meta‐analysis also demonstrated that therapy for infertility could increase the risk of thyroid cancer by approximately 35% .…”

Section: Discussionmentioning

confidence: 99%

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Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan

Ding

Chen

Wang

et al. 2019

Cancer

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Background The current study evaluated whether the risk of developing thyroid cancer in Asian women was associated with infertility and the use of fertility drugs. Methods The authors conducted a large, retrospective cohort study using Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,356 women aged 20 to 49 years who were diagnosed with infertility from 2000 through 2013 were included in the infertile group, and 53,424 women without a history of infertility were selected as fertile comparisons and were frequency matched by age and year of diagnosis. Both groups were followed up to 2013 to calculate incident thyroid cancer. Poisson regression analysis was used to estimate the incidence rate ratio (IRR). Results The incidence of thyroid cancer was 1.9‐fold greater in the infertile group compared with the comparison group (2.85 vs 1.53 per 10,000 person‐years), with an adjusted IRR of 1.80 (95% confidence interval [95% CI], 1.70‐1.92) for the infertile group. Higher cancer incidence was demonstrated for the infertile group after 7 years of follow‐up, with an adjusted IRR of 4.39 (95% CI, 4.03‐4.78) compared with the comparison group. Among infertile women, those who had taken the fertility drug clomiphene were found to have a reduced incidence of thyroid cancer compared with those who were treated without the drug (2.69 vs 3.42 per 10,000 person‐years), with an adjusted IRR of 0.86 (95% CI, 0.75‐0.99). However, the cancer incidence in infertile women being treated with clomiphene was nearly 6‐fold greater than that in fertile women taking the drug. Conclusions The results of the current study provide evidence that women with infertility are at an increased risk of developing thyroid cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan

Ding

Chen

Wang

et al. 2019

Cancer

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“…Ovarian stimulation has been shown to cause elevated levels of TSH (54) which promotes cellular proliferation in the gland. Both the normal thyroid gland and thyroid tumors exhibit estrogen receptors (55), although the exact mechanisms by which tumor growth is promoted are unclear (56). Thyroid cancer incidence has increased in recent years, possibly due to incidental findings of tumors with increased use of ultrasound, CT and MRI, however, when correcting for this in our analyses, risk was still elevated among ART women.…”

Section: Discussionmentioning

confidence: 99%

Cancer Risk in Women Treated with Fertility Drugs According to Parity Status—A Registry-based Cohort Study

Reigstad

Storeng

Myklebust

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Long-term safety of assisted reproductive techniques (ART) is of interest as use is increasing. Cancer risk is known to be affected by parity. This study examined risk of cancer after fertility treatment, stratified by women’s parity. Methods Data was obtained on all women (n=1 353 724) born in Norway between 1960–1996. Drug exposure data (2004–2014) was obtained from the Norwegian Prescription Database [drugs used in ART and clomiphene citrate (CC)]. The Medical Birth Registry of Norway provided parity status. Hazard ratios were calculated for all site cancer, breast, cervical, endometrial, ovarian, colorectal, central nervous system, thyroid cancer and malignant melanoma. Results In 12 354 392 person-years of follow-up, 20 128 women were diagnosed with cancer. All-site cancer risk was (1.14, 1.03–1.26) and (1.10, 0.98–1.23) following CC and ART exposure respectively. For ovarian cancer, a stronger association was observed for both exposures in nulliparous (HR 2.49, 1.30–4.78, and HR 1.62, 0.78–3.35) versus parous women (HR 1.37, 0.64–2.96, and HR 0.87, 0.33–2.27). Elevated risk of endometrial cancers was observed for CC exposure in nulliparous women (4.59, 2.68–7.84 vs. 1.44, 0.63–3.31). Risk was elevated for breast cancer in parous women exposed to CC (1.26, 1.03–1.54) and among nulliparous women after ART treatment (2.19, 1.08–4.44). Conclusion CC appears associated with increased risk of ovarian and endometrial cancer. Elevations in risks of breast and thyroid cancer were less consistent across type of drug exposure and parity. Impact Continued monitoring of fertility treatments is warranted.

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“…Collectively, these studies suggest a specific role for sex hormones, and in particular for Estrogen, in regulating thyroid function. In recent years different researchers have begun to examine the estrogen role in the development of thyroid pathologies [9,28]. Estrogen is known to be involved in cellular processes such as growth, cell motility and organ function.…”

Section: Introductionmentioning

confidence: 99%

Estrogen and thyroid cancer is a stem affair: A preliminary study

Zane

Parello

Pennelli

et al. 2017

Biomedicine & Pharmacotherapy

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Gender influences Papillary Thyroid Cancer (PTC) with an incidence of 3:1 when comparing women to men with different aggressiveness. This gender discrepancy suggests some role of sex hormones in favoring the malignant progression of thyroid tissue to cancer. Estrogens are known to promote Stem Cell self-renewal and, therefore, may be involved in tumor initiation. The goals of these studies are to investigate the underlying causes of gender differences in PTC by studying the specific role of estrogens on tumor cells and their involvement within the Cancer Stem Cell (CSC) compartment. Exposure to 1 nmol l−1 Estradiol for 24 h promotes growth and maintenance of PTC Stem Cells, while inducing dose-dependent cellular proliferation and differentiation following Estradiol administration. Whereas mimicking a condition of hormonal imbalance led to an opposite phenotype compared to a continuous treatment. In vivo we find that Estradiol promotes motility and tumorigenicity of CSCs. Estradiol-treated mice inoculated with Thyroid Cancer Stem Cell-enriched cells developed larger tumor masses than control mice. Furthermore, Estradiol-pretreated Cancer Stem cells migrated to distant organs, while untreated cells remained circumscribed. We also find that the biological response elicited by estrogens on Papillary Thyroid Cancer in women differed from men in pathways mediated. This could explain the gender imbalance in tumor incidence and development and could be useful to develop gender specific treatment of (PTC).

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Estrogens and Stem Cells in Thyroid Cancer

Cited by 18 publications

References 99 publications

Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan

Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan

Cancer Risk in Women Treated with Fertility Drugs According to Parity Status—A Registry-based Cohort Study

Estrogen and thyroid cancer is a stem affair: A preliminary study

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