Thyroid Cancers

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 39073

Special Issue Editor


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Guest Editor
Azienda Ospedaliera Universitaria "San Giovanni di Dio e Ruggi d' Aragona", UOC Clinica Endocrinologica e Diabetologica, Salerno, Italy
Interests: thyroid nodule; thyroid cancer; thyroid diseases; thyroid carcinogenesis; targeted therapy; molecular diagnostics

Special Issue Information

Dear Colleagues,

Thyroid cancers, including a heterogeneous set of tumors, are the most common endocrine malignancies. Furthermore, the thyroid cancer epidemiologic trend is a concern for public health systems worldwide, due not only to the dramatic incidence increase (more than triplicated from 1974–1977 to 2010–2013), but also to the low but continuous rise of mortality (1.1% per year from 1994 to 2013). This evolving scenario makes it mandatory to improve knowledge of disease etiology and biology in order to optimize prevention and the therapeutic approach. 

Thyroid cancer genetics has been deeply studied in the last 3 decades, leading to the identification of the casual mutational hit for the vast majority of patients. However, the real biological meaning of thyroid-cancer-related mutations is still debated. Therefore, the proper application of such genetic alterations into clinical practice, from diagnosis to therapeutic planning, needs to be refined. Furthermore, despite the deep characterization of underlying genetics, the etiology of thyroid cancer is currently unknown for the vast majority of patients. Indeed, the only factor having a well-characterized role in thyroid carcinogenesis is exposure to ionizing radiation, which accounts just for a niche of thyroid malignancies. Therefore, bridging the gap in thyroid cancer etiology represents a mandatory target for thyroid cancer research.

We particularly welcome contributions on all aspects related to thyroid tumors, including those of follicular origin and medullary thyroid cancer, in the form of either original research articles, concise reviews, or shorter perspective articles. We especially welcome articles dealing with a) the application of molecular genetics into clinical practice, including targeted therapies of aggressive thyroid cancers; and b) the understanding of thyroid cancer etiology.

Prof. Vincenzo Marotta
Guest Editor

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Published Papers (12 papers)

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Research

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8 pages, 1054 KiB  
Article
Predictors of Recurrence in Patients with Papillary Thyroid Carcinoma: Does Male Sex Matter?
by Hyeji Kim, Hyungju Kwon and Byung-In Moon
Cancers 2022, 14(8), 1896; https://doi.org/10.3390/cancers14081896 - 9 Apr 2022
Cited by 9 | Viewed by 1641
Abstract
Male patients with papillary thyroid carcinoma (PTC) usually have aggressive clinicopathological features, including large tumor size and lymph node metastasis; however, it is unclear whether male sex increases the risk of recurrence. Here, we evaluated the effect of sex on disease-free survival (DFS) [...] Read more.
Male patients with papillary thyroid carcinoma (PTC) usually have aggressive clinicopathological features, including large tumor size and lymph node metastasis; however, it is unclear whether male sex increases the risk of recurrence. Here, we evaluated the effect of sex on disease-free survival (DFS) of patients with PTC. Between 2009 and 2016, 1252 patients who underwent total thyroidectomy for PTC were enrolled; 157 (12.5%) were male and 1095 (87.5%) were female. With a mean follow-up of 6.6 years, five-year DFS rates were comparable between male and female patients (94.9% vs. 96.9%; p = 0.616) after adjusting for potential confounders. Multivariate Cox regression analysis also demonstrated that male sex was not an independent risk factor for recurrence (HR 1.982, 95% CI 0.831–4.726). Subgroup analyses further indicated that both male and female sex—in terms of their associations with five-year DFS—were comparable with other variables, including age < 55 years (94.5% vs. 97.3%; p = 0.520) and tumor size > 1 cm (91.9% vs. 97.0%; p = 0.243). In conclusion, male sex was not associated with the risk of recurrence in patients with PTC. Male patients do not always require aggressive treatment and follow-up approaches. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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15 pages, 18210 KiB  
Article
Downregulation and Hypermethylation of GABPB1 Is Associated with Aggressive Thyroid Cancer Features
by Xiangling Xing, Ninni Mu, Xiaotian Yuan, Na Wang, C. Christofer Juhlin, Klas Strååt, Catharina Larsson, Shi Yong Neo and Dawei Xu
Cancers 2022, 14(6), 1385; https://doi.org/10.3390/cancers14061385 - 8 Mar 2022
Cited by 6 | Viewed by 2412
Abstract
Promoter mutations of the telomerase reverse transcriptase (TERT) gene occur frequently in thyroid carcinoma (TC), including papillary (PTC) and anaplastic subtypes (ATC). Given that the ETS family transcription factors GABPA and GABPB1 activate the mutant TERT promoter and induce TERT expression [...] Read more.
Promoter mutations of the telomerase reverse transcriptase (TERT) gene occur frequently in thyroid carcinoma (TC), including papillary (PTC) and anaplastic subtypes (ATC). Given that the ETS family transcription factors GABPA and GABPB1 activate the mutant TERT promoter and induce TERT expression for telomerase activation, GABPB1 has been proposed as a cancer therapeutic target to inhibit telomerase. Here, we sought to determine the role of GABPB1 in TC pathogenesis. In TC-derived cells carrying the mutated TERT promoter, GABPB1 knockdown led to diminished TERT expression but significantly increased invasive potentials in vitro and metastatic potential in a xenograft zebrafish model and altered expression of markers for epithelial-to-mesenchymal transition. GABPB1 expression was downregulated in aggressive TCs. Low GABPB1 expression correlated with its promoter hypermethylation, which in turn was also associated with shorter disease-free survival. Consistently, DNA methylation inhibitors enhanced GABPB1 expression, as observed upon reduced promoter methylation. Our results suggest that GABPB1 is required for TERT expression and telomerase activation, but itself serves as a tumor suppressor to inhibit TC progression. Furthermore, aberrant DNA methylation leads to GABPB1 silencing, thereby promoting TC aggressiveness. Thus, caution is needed if targeting GABPB1 for cancer therapy is considered. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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10 pages, 616 KiB  
Article
A Three-Domain Scoring System to Customize the Risk of Relapse of Differentiated Thyroid Carcinoma
by Arnoldo Piccardo, Giacomo Siri, Martina Ugolini, Francesco Fiz, Matteo Puntoni, Gianluca Bottoni, Ugo Catrambone, Fabián Pitoia and Pierpaolo Trimboli
Cancers 2021, 13(17), 4335; https://doi.org/10.3390/cancers13174335 - 27 Aug 2021
Cited by 2 | Viewed by 2601
Abstract
Purpose: the validation of a new scoring model considering the principal risk factors of differentiated thyroid cancer (DTC) relapse. Methods: we evaluated all DTC patients treated with thyroidectomy and radioactive iodine (RAI) therapy. Three domains were considered: the demographic domain (age and gender), [...] Read more.
Purpose: the validation of a new scoring model considering the principal risk factors of differentiated thyroid cancer (DTC) relapse. Methods: we evaluated all DTC patients treated with thyroidectomy and radioactive iodine (RAI) therapy. Three domains were considered: the demographic domain (age and gender), the surgical domain (histology and the American Thyroid Association risk categories), and the RAI-related domain (pre-RAI thyroglobulin and post-therapeutic 131I whole-body scan). The progression-free survival was assessed. The patients’ sample was randomly split into a training and validation set. The three-domain score was calculated as the weighted sum of the levels of each significant factor, then scaled to an integer range (0–100) and, finally, stratified into terciles: mild risk 0–33, moderate risk 34–66, and severe risk 67–100. Results: 907 DTC patients were included. The RAI-related domain was the most relevant factor in the score calculation. The tercile stratification identified significantly different survival curves: patients within the two upper terciles showed approximately 6 to 30 times more progressive risk than patients at mild risk. Conclusion: we have validated a three-domain scoring system and the principal impact on this score is provided by the peri-RAI findings, whose prognostic role seems to be essential in risk identification. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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10 pages, 1092 KiB  
Article
Survival and Death Causes in Thyroid Cancer in Taiwan: A Nationwide Case–Control Cohort Study
by Yu-Ling Lu, Shu-Fu Lin, Ming-Hsien Wu, Yi-Yin Lee, Pai-Wei Lee, Shang-Hung Chang and Yu-Tung Huang
Cancers 2021, 13(16), 3955; https://doi.org/10.3390/cancers13163955 - 5 Aug 2021
Cited by 3 | Viewed by 2350
Abstract
The incidence of thyroid cancer has increased substantially worldwide. However, the overall mortality risk and actual causes of death in thyroid cancer patients have not been extensively evaluated. In this study, patients with thyroid cancer diagnosed between 2001 and 2017 were analyzed from [...] Read more.
The incidence of thyroid cancer has increased substantially worldwide. However, the overall mortality risk and actual causes of death in thyroid cancer patients have not been extensively evaluated. In this study, patients with thyroid cancer diagnosed between 2001 and 2017 were analyzed from Taiwan’s National Health Insurance Research Database. We compared these patients with control subjects matched for age, gender, history of cardiovascular disease (CVD), hyperlipidemia, diabetes mellitus, hypertension, and occupation to assess the risk of overall mortality and cause-specific mortality. Finally, our cohort comprised 30,778 patients with thyroid cancer. Three hundred and ninety-eight deaths (1.29%) occurred during a median follow-up of 60.0 months (range: 30.3 to 117.6 months). The primary cause of death was thyroid cancer mortality (31.2%), followed by other malignancy-related mortality (29.9%) and CVD mortality (12.3%). The overall mortality risk was similar between the thyroid cancer and control groups (unadjusted hazard ratio (HR): 0.98; 95% confidence interval (CI): 0.88–1.10); the adjusted HR was 1.07 (95% CI: 0.95–1.20) after multivariate adjustment for age, gender, history of CVD, hyperlipidemia, diabetes mellitus, hypertension, and occupation. The risk of other malignancy-related mortality was comparable between two groups. CVD mortality risk was lower in the thyroid cancer group, with an unadjusted HR of 0.51 (95% CI: 0.38–0.69) and adjusted HR of 0.56 (95% CI: 0.42–0.76). In conclusion, patients with thyroid cancer had excellent overall survival. Thyroid cancer-specific mortality was the leading cause of death, highlighting the importance of thyroid cancer management. Thyroid cancer patients had lower CVD mortality risk than the general population. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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15 pages, 10845 KiB  
Article
Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome
by Lorenza Mautone, Carlo Ferravante, Anna Tortora, Roberta Tarallo, Giorgio Giurato, Alessandro Weisz and Mario Vitale
Cancers 2021, 13(12), 2937; https://doi.org/10.3390/cancers13122937 - 11 Jun 2021
Cited by 13 | Viewed by 3207
Abstract
Integrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the expression pattern of integrin family subunits in [...] Read more.
Integrins are cell-extracellular matrix adhesion molecules whose expression level undergoes quantitative changes upon neoplastic transformation and are considered functionally related to the development of cancer metastasis. We analyzed the largest mRNA-seq dataset available to determine the expression pattern of integrin family subunits in papillary thyroid carcinomas (PTC). ITGA2, 3, 6, V, and ITGB1 integrin subunits were overexpressed in PTC compared to normal thyroid tissue. The PTC histology variants “classical” and “tall cell” displayed a similar integrin expression profile with a higher level of ITGA3, ITGAV, and ITGB1, which differed from that of the “follicular” variant. Interestingly, compared to RAS mutations, BRAFV600E mutation was associated with a significantly higher expression of integrins. Some integrin subunits were associated with advanced disease stage, lymph node metastasis, extrathyroidal extension, and high-risk groups. Among them, ITGA3 expression displayed the highest correlation with advanced disease and was associated with a negative prognosis. In vitro scratch assay and Matrigel invasion assay in two different PTC cell lines confirmed α3β1 role in cell motility and invasion, supporting its involvement during tumor progression. These results demonstrate the existence of a PTC-specific integrin expression signature correlated to histopathology, specific driver gene mutations, and aggressiveness of the disease. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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24 pages, 5243 KiB  
Article
Gold-Based Nanoplataform for the Treatment of Anaplastic Thyroid Carcinoma: A Step Forward
by Mariana Amaral, Adília J. Charmier, Ricardo A. Afonso, José Catarino, Pedro Faísca, Lina Carvalho, Lia Ascensão, João M. P. Coelho, M. Manuela Gaspar and Catarina Pinto Reis
Cancers 2021, 13(6), 1242; https://doi.org/10.3390/cancers13061242 - 12 Mar 2021
Cited by 23 | Viewed by 3714
Abstract
Anaplastic thyroid carcinoma (ATC) is a very rare subtype of thyroid carcinoma and one of the most lethal malignancies. Poor prognosis is mainly associated with its undifferentiated nature, inoperability, and failing to respond to the typically used therapies for thyroid cancer. Photothermal Therapy [...] Read more.
Anaplastic thyroid carcinoma (ATC) is a very rare subtype of thyroid carcinoma and one of the most lethal malignancies. Poor prognosis is mainly associated with its undifferentiated nature, inoperability, and failing to respond to the typically used therapies for thyroid cancer. Photothermal Therapy (PTT) entails using light to increase tissues’ temperature, leading to hyperthermia-mediated cell death. Tumours are more susceptible to heat as they are unable to dissipate it. By using functionalized gold nanoparticles (AuNPs) that transform light energy into heat, it is possible to target the heat to the tumour. This study aims to formulate ATC-targeted AuNPs able to convert near-infrared light into heat, for PTT of ATC. Different AuNPs were synthetized and coated. Size, morphology, and surface plasmon resonances band were determined. The optimized coated-AuNPs were then functionalized with ligands to assess ATC’s specificity. Safety, efficacy, and selectivity were assessed in vitro. The formulations were deemed safe when not irradiated (>70% cell viability) and selective for ATC. However, when irradiated, holo-transferrin-AuNPs were the most cytotoxic (22% of cell viability). The biodistribution and safety of this formulation was assessed in vivo. Overall, this novel formulation appears to be a highly promising approach to evaluate in a very near future. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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24 pages, 348 KiB  
Article
Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma
by Danuta Gąsior-Perczak, Artur Kowalik, Krzysztof Gruszczyński, Agnieszka Walczyk, Monika Siołek, Iwona Pałyga, Sławomir Trepka, Estera Mikina, Tomasz Trybek, Janusz Kopczyński, Agnieszka Suligowska, Rafał Ślusarczyk, Agnieszka Gonet, Jarosław Jaskulski, Paweł Orłowski, Magdalena Chrapek, Stanisław Góźdź and Aldona Kowalska
Cancers 2021, 13(3), 470; https://doi.org/10.3390/cancers13030470 - 26 Jan 2021
Cited by 6 | Viewed by 2809
Abstract
The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse [...] Read more.
The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease. Full article
(This article belongs to the Special Issue Thyroid Cancers)

Review

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18 pages, 738 KiB  
Review
Cell-Free DNA Analysis within the Challenges of Thyroid Cancer Management
by Vincenzo Marotta, Michele Cennamo, Evelina La Civita, Mario Vitale and Daniela Terracciano
Cancers 2022, 14(21), 5370; https://doi.org/10.3390/cancers14215370 - 31 Oct 2022
Cited by 4 | Viewed by 1828
Abstract
Thyroid cancer is the most frequent endocrine malignancy with an increasing incidence trend during the past forty years and a concomitant rise in cancer-related mortality. The circulating cell-free DNA (cfDNA) analysis is a patient’s friendly and repeatable procedure allowing to obtain surrogate information [...] Read more.
Thyroid cancer is the most frequent endocrine malignancy with an increasing incidence trend during the past forty years and a concomitant rise in cancer-related mortality. The circulating cell-free DNA (cfDNA) analysis is a patient’s friendly and repeatable procedure allowing to obtain surrogate information about the genetics and epigenetics of the tumor. The aim of the present review was to address the suitability of cfDNA testing in different forms of thyroid cancer, and the potential clinical applications, as referred to the clinical weaknesses. Despite being limited by the absence of standardization and by reproducibility and validity issues, cfDNA assessment has great potential for the improvement of thyroid cancer management. cfDNA may support the pre-surgical definition of thyroid nodules by complementing invasive thyroid fine needle aspiration cytology. In addition, it may empower risk stratification and could be used as a biomarker for monitoring the post-surgical disease status, both during active surveillance and in the case of anti-tumor treatment. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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18 pages, 1705 KiB  
Review
Heavy Metals in the Environment and Thyroid Cancer
by Fiorenza Gianì, Roberta Masto, Maria Antonietta Trovato, Pasqualino Malandrino, Marco Russo, Gabriella Pellegriti, Paolo Vigneri and Riccardo Vigneri
Cancers 2021, 13(16), 4052; https://doi.org/10.3390/cancers13164052 - 12 Aug 2021
Cited by 39 | Viewed by 5831
Abstract
In recent decades, the incidence of thyroid cancer has increased more than most other cancers, paralleling the generalized worldwide increase in metal pollution. This review provides an overview of the evidence supporting a possible causative link between the increase in heavy metals in [...] Read more.
In recent decades, the incidence of thyroid cancer has increased more than most other cancers, paralleling the generalized worldwide increase in metal pollution. This review provides an overview of the evidence supporting a possible causative link between the increase in heavy metals in the environment and thyroid cancer. The major novelty is that human thyroid stem/progenitor cells (thyrospheres) chronically exposed to different metals at slightly increased environmentally relevant concentrations show a biphasic increase in proliferation typical of hormesis. The molecular mechanisms include, for all metals investigated, the activation of the extracellular signal-regulated kinase (ERK1/2) pathway. A metal mixture, at the same concentration of individual metals, was more effective. Under the same conditions, mature thyrocytes were unaffected. Preliminary data with tungsten indicate that, after chronic exposure, additional abnormalities may occur and persist in thyrocytes derived from exposed thyrospheres, leading to a progeny population of transformation-prone thyroid cells. In a rat model predisposed to develop thyroid cancer, long-term exposure to low levels of metals accelerated and worsened histological signs of malignancy in the thyroid. These studies provide new insight on metal toxicity and carcinogenicity occurring in thyroid cells at a low stage of differentiation when chronically exposed to metal concentrations that are slightly increased, albeit still in the “normal” range. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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16 pages, 625 KiB  
Review
Significance of RAS Mutations in Thyroid Benign Nodules and Non-Medullary Thyroid Cancer
by Vincenzo Marotta, Maurizio Bifulco and Mario Vitale
Cancers 2021, 13(15), 3785; https://doi.org/10.3390/cancers13153785 - 27 Jul 2021
Cited by 46 | Viewed by 5103
Abstract
Thyroid nodules are detected in up to 60% of people by ultrasound examination. Most of them are benign nodules requiring only follow up, while about 4% are carcinomas and require surgery. Malignant nodules can be diagnosed by the fine-needle aspiration cytology (FNAC), which [...] Read more.
Thyroid nodules are detected in up to 60% of people by ultrasound examination. Most of them are benign nodules requiring only follow up, while about 4% are carcinomas and require surgery. Malignant nodules can be diagnosed by the fine-needle aspiration cytology (FNAC), which however yields an indeterminate result in about 30% of the cases. Testing for RAS mutations has been proposed to refine indeterminate cytology. However, the new entity of non-invasive follicular thyroid neoplasm, considered as having a benign evolution and frequently carrying RAS mutations, is expected to lower the specificity of this mutation. The aggressive behavior of thyroid cancer with RAS mutations, initially reported, has been overturned by the recent finding of the cooperative role of TERT mutations. Although some animal models support the carcinogenic role of RAS mutations in the thyroid, evidence that adenomas harboring these mutations evolve in carcinomas is lacking. Their poor specificity and sensitivity make the clinical impact of RAS mutations on the management of thyroid nodules with indeterminate cytology unsatisfactory. Evidence suggests that RAS mutation-positive benign nodules demand a conservative treatment. To have a clinical impact, RAS mutations in thyroid malignancies need not to be considered alone but rather together with other genetic abnormalities in a more general context. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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15 pages, 775 KiB  
Review
Genetics of Familial Non-Medullary Thyroid Carcinoma (FNMTC)
by Chiara Diquigiovanni and Elena Bonora
Cancers 2021, 13(9), 2178; https://doi.org/10.3390/cancers13092178 - 30 Apr 2021
Cited by 8 | Viewed by 3322
Abstract
Non-medullary thyroid carcinoma (NMTC) is the most frequent endocrine tumor and originates from the follicular epithelial cells of the thyroid. Familial NMTC (FNMTC) has been defined in pedigrees where two or more first-degree relatives of the patient present the disease in absence of [...] Read more.
Non-medullary thyroid carcinoma (NMTC) is the most frequent endocrine tumor and originates from the follicular epithelial cells of the thyroid. Familial NMTC (FNMTC) has been defined in pedigrees where two or more first-degree relatives of the patient present the disease in absence of other predisposing environmental factors. Compared to sporadic cases, FNMTCs are often multifocal, recurring more frequently and showing an early age at onset with a worse outcome. FNMTC cases show a high degree of genetic heterogeneity, thus impairing the identification of the underlying molecular causes. Over the last two decades, many efforts in identifying the susceptibility genes in large pedigrees were carried out using linkage-based approaches and genome-wide association studies, leading to the identification of susceptibility loci and variants associated with NMTC risk. The introduction of next-generation sequencing technologies has greatly contributed to the elucidation of FNMTC predisposition, leading to the identification of novel candidate variants, shortening the time and cost of gene tests. In this review we report the most significant genes identified for the FNMTC predisposition. Integrating these new molecular findings in the clinical data of patients is fundamental for an early detection and the development of tailored therapies, in order to optimize patient management. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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Other

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16 pages, 5451 KiB  
Systematic Review
Risk of Adverse Pregnancy Outcomes in Young Women with Thyroid Cancer: A Systematic Review and Meta-Analysis
by Shinje Moon, Ka Hee Yi and Young Joo Park
Cancers 2022, 14(10), 2382; https://doi.org/10.3390/cancers14102382 - 12 May 2022
Cited by 8 | Viewed by 2533
Abstract
This meta-analysis investigated whether thyroidectomy or radioactive iodine treatment (RAIT) in patients with differentiated thyroid cancer (DTC) was associated with an increase in adverse pregnancy outcomes, such as miscarriage, preterm delivery, and congenital malformations. A total of 22 articles (5 case-control and 17 [...] Read more.
This meta-analysis investigated whether thyroidectomy or radioactive iodine treatment (RAIT) in patients with differentiated thyroid cancer (DTC) was associated with an increase in adverse pregnancy outcomes, such as miscarriage, preterm delivery, and congenital malformations. A total of 22 articles (5 case-control and 17 case series studies) from 1262 studies identified through a literature search in the PubMed and EMBASE databases from inception up to 13 September 2021 were included. In patients with DTC who underwent thyroidectomy, the event rates for miscarriage, preterm labor, and congenital anomalies were 0.07 (95% confidence interval [CI], 0.05–0.11; 17 studies), 0.07 (95% CI, 0.05–0.09; 14 studies), and 0.03 (95% CI, 0.02–0.06; 17 studies), respectively. These results are similar to those previously reported in the general population. The risk of miscarriage or abortion was increased in patients with DTC when compared with controls without DTC (odds ratio [OR], 1.80; 95% CI, 1.28–2.53; I2 = 33%; 3 studies), while the OR values for preterm labor and the presence of congenital anomalies were 1.22 (95% CI, 0.90–1.66; I2 = 62%; five studies) and 0.73 (95% CI, 0.39–1.38; I2 = 0%; two studies) respectively, which showed no statistical significance. A subgroup analysis of patients with DTC according to RAIT revealed that the risk of miscarriage, preterm labor, or congenital anomalies was not increased in the RAIT group when compared with patients without RAIT. The results of this meta-analysis suggest that thyroid cancer treatment, including RAIT, is not associated with an increased risk of adverse pregnancy outcomes, including miscarriage, preterm labor, and congenital anomalies. Full article
(This article belongs to the Special Issue Thyroid Cancers)
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