Background Thyroid cancer is the leading cause of mortality and morbidity among cancers of the endocrine system. We aimed to describe the trends of thyroid cancer burden in North Africa and Middle East for 1990–2019. Methods Data on burden of thyroid cancer in North Africa and Middle East from 1990 to 2019 were obtained from the Global Burden of Disease (GBD) Study 2019. Decomposition analysis was used to estimate the effects of population growth, aging, and change in incident numbers on overall change of thyroid cancer incidence. Also, we used the comparative risk assessment framework of GBD to determine the burden of thyroid cancer attributable to a high body mass index (BMI). Results In 2019, the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of thyroid cancer were 3.5 (2.9–4) and 0.5 (0.5–0.7) per 100,000, respectively. The highest age-standardized incidence, deaths, and disability-adjusted life year (DALY) rate were in Lebanon, Afghanistan, and United Arab Emirates, respectively. The ASIR of thyroid cancer in region was about 2.5 times higher among women, which had a positive association with increasing age. In 2019, the age-standardized deaths attributable to a high BMI was 16.7% of all deaths due to thyroid cancer. In 1990–2019, the overall change in thyroid cancer incident cases was a 396% increase which was mostly driven by the increase in disease-specific incidence rate (256.8%). Conclusions Women, the elderly above about 60 years old, and countries with a higher sociodemographic index showed higher incidence rates of thyroid cancer. Regarding our findings, it is recommended to establish preventive plans by modification in life style like weight reduction programs.

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Burden of thyroid cancer in North Africa and Middle East 1990–2019

Thyroid cancer (TC) represents the most common endocrine malignancy, with an increasing incidence all over the world. Papillary TC (PTC), a differentiated TC subtype, is the most common and, even though it has an excellent prognosis following radioiodine (RAI) ablation, it shows an aggressive behavior in 20–30% of cases, becoming RAI-resistant and/or metastatic. On the other side, anaplastic thyroid carcinoma (ATC), the most undifferentiated TC, is a rare but devastating disease, indicating that progression of differentiated to undifferentiated forms of TC could be responsible for RAI-resistance and increased mortality. The epithelial-to-mesenchymal transition (EMT) plays a pivotal role in both tumor progression and resistance to therapy. Moreover, during tumor progression, cancer cells modify their metabolism to meet changed requirements for cellular proliferation. Through these metabolic changes, cancer cells may adopt cancer stem cell-like properties and express an EMT phenotype. EMT, in turn, can induce metabolic changes to which cancer cells become addicted. Here we review metabolic reprogramming in TC highlighting the role of EMT with the aim to explore a potential field to find out new therapeutic strategies for advanced-stage PTC. Accordingly, we discuss the identification of the metabolic enzymes and metabolites, critical to TC progression, which can be employed either as predicting biomarkers of tumor response to RAI therapy or possible targets in precision medicine.

Metabolic Reprogramming in Thyroid Cancer: Role of the Epithelial-Mesenchymal Transition

An updated exploration of the burden of thyroid cancer across a country is always required for making correct decisions. The objective of this study is to present the thyroid cancer burden and attributed burden to the high Body Mass Index (BMI) in Iran at national and sub-national levels from 1990 to 2019. The data was obtained from the GBD 2019 study estimates. To explain the pattern of changes in incidence from 1990 to 2019, decomposition analysis was conducted. Besides, the attribution of high BMI in the thyroid cancer DALYs and deaths were obtained. The age-standardized incidence rate of thyroid cancer was 1.57 (95% UI: 1.33-1.86) in 1990 and increased 131% (53-191) until 2019. The age-standardized prevalence rate of thyroid cancer was 30.19 (18.75-34.55) in 2019 which increased 164% (77-246) from 11.44 (9.38-13.85) in 1990. In 2019, the death rate, and Disability-adjusted life years of thyroid cancer was 0.49 (0.36-0.53), and 13.16 (8.93-14.62), respectively. These numbers also increased since 1990. The DALYs and deaths attributable to high BMI was 1.91 (0.95-3.11) and 0.07 (0.04-0.11), respectively. The thyroid cancer burden and high BMI attributed burden has increased from 1990 to 2019 in Iran. This study and similar studies' results can be used for accurate resource allocation for efficient management and all potential risks' modification for thyroid cancer with a cost-conscious view. 

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National, sub-national, and risk-attributed burden of thyroid cancer in Iran from 1990 to 2019

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The early-stage diagnosis of papillary thyroid cancer (PTC) has significantly increased in incidence worldwide without any beneficial impact on survival. In order to improve the risk assessment in PTC, we have conducted a retrospective study in which we analyzed the BRAF V600E mutation and CPSF2 protein expression as prognostic markers on archival tissue samples of 49 patients without (control group) and 97 patients with (study group) PTC metastases in the cervical lymph nodes at the time of initial diagnosis. Our aim was to correlate the BRAF V600E mutation and the expression of CPSF2 protein with the clinical and pathological features of PTC. The expression of CPSF2 protein was evaluated via immunohistochemistry and graded semi-quantitatively. The presence of the BRAF V600E mutation was determined via real-time polymerase chain reac-tion (PCR). CPSF2 protein < 3+ intensity expression was correlated with more frequent recurrences (Fisher-Freeman-Halton exact test; p = 0.010; 95% CI: 1.26–22.03), and patients who presented with the BRAF V600E mutation and CPSF2 protein expression < 3+ intensity had shorter disease-free survival (log-rank test; 105.0 months vs. 146.6 months; p < 0.001; HR 8.32, 95% CI: 2.91–23.83), whereas patients with PTC who had CPSF2 expression 3+ had longer disease-free survival in correlation with other lower intensity expressions of CPSF2 protein (log-rank test; 139.7 months vs. 129.6 months; p = 0.008). The multivariate analysis showed that younger patients with CPSF2 protein expression <3+ and the BRAF V600E mutation are at an increased risk for recurrence and require more intensive monitoring (Cox proportional hazards regression model; X2 = 17.5, df = 10, p = 0.025). Our results correlate the BRAF V600E mutation and CPSF2 protein expression with recurrence and disease-free survival as relevant prognostic factors for PTC.

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Prognostic Significance of BRAF V600E Mutation and CPSF2 Protein Expression in Papillary Thyroid Cancer

Background To investigate the burden of thyroid cancer and its attributable risk factors in 204 countries and territories during 30 years. Methods We extracted data from the Global Burden of Disease (GBD) 2019 database, including incidence, mortality, disability-adjusted life-years (DALYs), and the attributable risk factors of thyroid cancer from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). We also examined the associations between cancer burden and the sociodemographic index (SDI). Results The global new cases, death, and DALYs of thyroid cancer in 2019 were 233 847 (95% UI: 211 637-252 807), 45 576 (95% UI: 41 290-48 775), and 1 231 841 (95% UI: 1 113 585-1 327 064), respectively. From 1990 to 2019, the ASIR of thyroid cancer showed an upward trend (EAPC = 1.25), but ASMR (EAPC = -0.15) and ASDR (EAPC = -0.14) decreased. The burden of thyroid cancer varied at regional and national levels, but the association between ASIR and SDI was positive. We found that the burden of thyroid cancer was mainly concentrated in females and that the age of onset tended to be younger. The proportion of DALYs from thyroid cancer attributable to high body-mass index was higher in high SDI regions, especially in males. Conclusions The global incidence of thyroid cancer has continued to increase in the past three decades. The high body-mass index as an important risk factor for thyroid cancer deserves greater attention, especially in high SDI regions.

Hao Zi

Papers

Global burden of thyroid cancer and its attributable risk factors in 204 countries and territories from 1990 to 2019.