Dataset Information

Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

ABSTRACT:

Backgruound

Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC.

Methods

This study included two types of research.

Results

retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study with the NEST data and eight selected studies.

Results

Of the 4,398 patients with DTC in NEST, 341 patients (7.8%) died during the median follow-up period of 15 years (interquartile range, 12.3 to 15.6). Of these, 91 deaths (2.1%) were related to DTC. HT was associated with a smaller tumor size and less aggressive DTC. In Cox regression analysis after adjusting for age and sex, patients with HT showed a significantly lower risk of all-cause death (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52 to 0.96) and DTC-related death (HR, 0.33; 95% CI, 0.14 to 0.77). The analysis with inverse probability of treatment weight data adjusted for age, sex, and year of thyroid cancer registration showed similar association. The meta-analysis showed that patients with HT showed a lower risk of all-cause mortality (risk ratio [RR], 0.24; 95% CI, 0.13 to 0.47) and thyroid cancer-related mortality (RR, 0.23; 95% CI, 0.13 to 0.40) in comparison with patients without HT.

Conclusion

This study showed that DTC co-presenting with HT is associated with a low risk of advanced DTC and presents a low risk for all-cause and DTC-related death.

SUBMITTER: Yang I

PROVIDER: S-EPMC10901652 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

Yang Injung I Yu Jae Myung JM Chung Hye Soo HS Kim Yoon Jung YJ Roh Yong Kyun YK Choi Min Kyu MK Park Sung-Ho SH Park Young Joo YJ Moon Shinje S

Endocrinology and metabolism (Seoul, Korea) 20240103 1

<h4>Backgruound</h4>Many studies have shown that Hashimoto's thyroiditis (HT) acts as a protective factor in differentiated thyroid cancer (DTC), but little is known about its effects on mortality. Therefore, this study was performed to reveal the prognosis of HT on mortality in patients with DTC.<h4>Methods</h4>This study included two types of research.<h4>Results</h4>retrospective cohort study using the National Epidemiologic Survey of Thyroid cancer (NEST) in Korea and meta-analysis study wit ...[more]

PMID: 38171210

Similar Datasets

Project description:Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)-adjusted p-value ≤ 0.05 and a fold change (FC) > 2, four comparison groups were defined, which were HT vs. TN; PTC w/ HT vs. TN; PTC w/o HT vs. TN; and mPTC vs. TN. A Venn diagram displayed 15 different intersecting and non-intersecting differentially expressed gene (DEG) sets, of which a set of 71 DEGs, shared between the two comparison groups HT vs. TN ∩ PTC w/ HT vs. TN, harbored the relatively largest number of genes related to immune and inflammatory functions; oxidative stress and reactive oxygen species (ROS); DNA damage and DNA repair; cell cycle; and apoptosis. The majority of the 71 DEGs were upregulated and the most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6). Upregulated genes preferentially associated with other gene ontologies (GO) were, e.g., STAT1, MMP9, TOP2A, and BRCA2. Biofunctional analysis revealed pathways related to immunogenic functions. Further data analysis focused on the set of non-intersecting 358 DEGs derived from the comparison group of HT vs. TN, and on the set of 950 DEGs from the intersection of all four comparison groups. In conclusion, this study indicates that, besides immune/inflammation-related genes, also genes associated with oxidative stress, ROS, DNA damage, DNA repair, cell cycle, and apoptosis are comparably more deregulated in a data set shared between HT and PTC w/ HT. These findings are compatible with the conception of a genetic sequence where chronic inflammatory response is accompanied by deregulation of genes and biofunctions associated with oncogenic transformation. The generated data set may serve as a source for identifying candidate genes and biomarkers that are practical for clinical application.

Project description:ImportanceHashimoto thyroiditis (HT) has been suggested to be associated with papillary thyroid cancer (PTC) development. However, its association with PTC progression remains unclear.ObjectiveTo examine the association between HT and PTC presentation and outcomes.Design, setting, and participantsThis retrospective cohort study included a review of patients aged 18 to 75 years who had pathologically confirmed PTC treated at a single center in China from January 1, 2001, to December 31, 2014. Data analysis was performed from November 1 to December 31, 2020.ExposuresCoexistent HT was defined according to evaluation of postoperative paraffin sections.Main outcomes and measuresThe primary outcome was the association of HT with PTC-related mortality, assessed using Cox proportional hazards regression models. The secondary outcome was the association of HT with aggressive characteristics and structural recurrence of PTC, assessed using logistic regression and Cox proportional hazards regression with and without adjustment for related factors.ResultsOf 9210 patients with PTC (mean [SD] age, 43.6 [12.0] years; 6872 [75%] women) included in the analysis, 1751 (19%) had HT. In the logistic regression model, HT was negatively associated with frequencies of primary tumor size of 4 cm or greater (adjusted odds ratio [aOR], 0.20; 95% CI, 0.12-0.33; P < .001), gross extrathyroidal extension (aOR, 0.44; 95% CI, 0.36-0.54; P < .001), extranodal extension (aOR, 0.66; 95% CI, 0.55-0.80; P < .001), and distant metastasis (aOR, 0.17; 95% CI, 0.04-0.71; P = .02). After a median follow-up of 85 months (range, 12-144 months), 131 PTC-related deaths were identified in the cohort; 2 patients who died had HT. Patients with HT had significantly superior outcomes compared with patients without HT in terms of unadjusted 10-year disease-specific survival (99.9% vs 96.6%; log-rank P < .001) and recurrence-free survival (92.0% vs 87.6%; log-rank P = .001). After adjusting for sex, age, primary tumor size, extrathyroidal extension, lymph node metastasis, distant metastasis, extent of surgery, and radioactive iodine ablation, HT was associated with decreased PTC-related mortality (hazard ratio [HR], 0.19; 95% CI, 0.05-0.76; P = .02). Stratified analysis showed that HT was associated with less frequent structural recurrence in patients with extrathyroidal extension (HR, 0.52; 95% CI, 0.38-0.71; P < .001; P = .002 for interaction) or after total thyroidectomy (HR, 0.50; 95% CI, 0.35-0.69; P < .001; P = .009 for interaction).Conclusions and relevanceIn this cohort study, patients with coexistent HT had less aggressive characteristics at presentation and better outcomes of PTC than did patients without HT. The findings suggest that autoimmune thyroiditis has a protective role in association with thyroid cancer.

Project description:Background: Protective effects of vitamin D have been reported in autoimmune and malignant thyroid diseases, though little is known about the underlying mechanism. Sirtuin 1 histon deacethylase (SIRT1) links the vitamin D pathway with regulation of transcription factor FOXO3a, a key player in cell cycle regulation and apoptosis. Aim of the present study was to investigate common single nucleotide polymorphisms (SNP's) in FOXO3a gene in respect to thyroid diseases, as well as to evaluate the hypothesis of Sirtuin1-FOXO3a interaction being a mediator of anti-proliferative vitamin D effects. Methods: The SNP's FOXO3a rs4946936/rs4945816/rs9400239 were genotyped in 257 patients with differentiated thyroid carcinoma (DTC), 139 patients with Hashimoto thyroiditis (HT) and 463 healthy controls (HC). Moreover, T-helper cells of HC and papillary thyroid cancer cell line BCPAP were incubated with 1,25(OH)2D3 and/or SIRT1 inhibitor Ex-527 in order to elucidate SIRT1- dependent vitamin D effects on cell proliferation and FOXO3a gene expression in vitro. Results: Patients with DTC tended to carry more often allele C in FOXO3a rs4946936 in comparison to HC (pcorrected = pc = 0.08). FOXO3a rs9400239T and rs4945816C was more frequent in HT in comparison to HC (pc = 0.02 and pc = 0.01, respectively). In both DTC and HT, we could not find a correlation of FOXO3a SNP's with vitamin D status. However, on in vitro level, 1,25(OH)2D3 showed an anti-proliferative effect in both T-helper cells and BCPAP, that was blocked by SIRT1 inhibition (T-helper cells: p = 0.0059, BCPAP: p = 0.04) and accompanied by elevated FOXO3a gene expression in T-helper cells (p = 0.05). Conclusions: FOXO3a rs9400239T and rs4945816C may constitute risk factors for HT, independent of the vitamin D status.This indicates the implication of FOXO3a in pathogenesis of autoimmune thyroid diseases. The dependency of anti-proliferative vitamin D effects on SIRT1 activity further suggests a key role of vitamin D-SIRT1-FOXO3a axis for protective vitamin D effects.

Dataset Information

Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

Backgruound

Methods

Results

Results

Conclusion

Publications

Hashimoto Thyroiditis and Mortality in Patients with Differentiated Thyroid Cancer: The National Epidemiologic Survey of Thyroid Cancer in Korea and Meta-Analysis.

Similar Datasets

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