Association of High Iodine Intake with the T1799A BRAF Mutation in Papillary Thyroid Cancer

Abstract Context: Epidemiological studies have indicated that high iodine intake might be a risk factor for papillary thyroid cancer (PTC), which commonly harbors the oncogenic T1799A BRAF mutation. Objective: The objective of the study was to investigate the relationship between BRAF mutation in PTC and iodine intake in patients. Subjects and Methods: We analyzed and compared the prevalences of the T1799A BRAF mutation in classical PTC of 1032 patients from five regions in China that uniquely harbor different iodine contents in natural drinking water, ranging from normal (10–21 μg/liter) to high (104–287 μg/liter). The BRAF mutation was identified by direct DNA sequencing. Results: The prevalence of BRAF mutation was significantly higher in any of the regions with high iodine content than any of the regions with normal iodine content. Overall, BRAF mutation was found in 387 of 559 PTC with high iodine content (69%) vs. 252 of 473 PTC with normal iodine content (53%), with an odds ratio of 1.97 (95% confidence interval 1.53–2.55) for the association of BRAF mutation with high iodine content (P < 0.0001). In addition, clinicopathological correlation analysis, the largest one of its type ever, showed that BRAF mutation was significantly associated with extrathyroidal invasion, lymph node metastasis, and advanced tumor stages of PTC. Conclusions: High iodine intake seems to be a significant risk factor for the occurrence of BRAF mutation in thyroid gland and may therefore be a risk factor for the development of PTC. This large study also confirmed the association of BRAF mutation with poorer clinicopathological outcomes of PTC.

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Association of High Iodine Intake with the T1799A BRAF Mutation in Papillary Thyroid Cancer

Yearbook of Endocrinology ◽

10.1016/s0084-3741(10)79458-0 ◽

2010 ◽

Vol 2010 ◽

pp. 155-157

Author(s):

M. Schott

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Braf Mutation ◽

Iodine Intake ◽

Papillary Thyroid ◽

High Iodine

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Low urinary iodine is a protective factor of central lymph node metastasis in papillary thyroid cancer: a cross-sectional study

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02302-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Ziyang Zeng ◽

Kang Li ◽

Xianze Wang ◽

Siwen Ouyang ◽

Zimu Zhang ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Protective Factor ◽

Urinary Iodine ◽

Iodine Intake ◽

Clinicopathological Features ◽

Papillary Thyroid ◽

Central Lymph Node ◽

High Iodine ◽

Central Lymph

Abstract Background An abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients. Methods Three hundred and fifty-nine PTC patients who received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr), and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM). Results There were no significant differences in UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(−) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in the high-iodine group (p = 0.02). In addition, younger age, larger tumor size, and classic variant were positively correlated with CLNM (p < 0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 μg/L) was associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 μg/L and above requirements as ≥ 190 μg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR 0.53, 95% CI 0.31–0.91) and in PTC < 1 cm (papillary thyroid microcarcinoma, PTMC) (OR 0.43, 95% CI 0.21–0.87). Conclusions Low iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.

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Risk Factor Stratification of Lung Metastasis in Children and Adolescent Papillary Thyroid Cancer

10.21203/rs.3.rs-661514/v1 ◽

2021 ◽

Author(s):

Liying Wang ◽

Feng Liu ◽

Lingyun Zhang ◽

Shu Rui ◽

Yang Liu ◽

...

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Lung Metastasis ◽

Independent Risk Factor ◽

Significant Risk ◽

Response To Therapy ◽

Papillary Thyroid ◽

Children And Adolescent ◽

Factors Associated

Abstract Background: Lung metastasis (LM) in pediatric papillary thyroid cancer (pPTC) is significantly higher than in adults. While spare information about pPTC and LM hampers to formulate specific guideline. Hence, we retrospectively analyzed the whole pPTCs in our center to investigate factors associated with LM and therapy outcomes.Materials and Methods: PTCs with age＜20 years who received initial operations in ourcenterfrom December 2008 to December 2018 were retrospectively reviewed. Clinicopathological information, treatment pipelineand outcomes were analyzed retrospectively.Results:Totally, 114 pPTC patients were enrolled in our study, LM was observed in 17 (14.9 %) cases. Significant risk factors associated with LM were age, sex, tumor size, multifocality, extrathyroidal extension, lymph node metastasis, number of metastatic lymph nodes (NMLNs)and postoperative stimulated thyroglobulin (sTg). NMLNs ＞14 was identified as an independent risk factor for LM by multivariate analysis (OR 25.166, 95% CI 2.814 - 225.009, p = 0.004) with a sensitivity of 86.7% and specificity of 81.1% for LM, which was verified by integrated meta-analysis. In terms ofresponse to radioiodine treatment in LM, 2 cases reached ‘‘excellent’’ response. ‘‘Biochemically incomplete’’, ‘‘structurally incomplete’’ and “indeterminate” were in 3,12, 2 of 17 patients respectively. Postoperative sTg was correlated with the response to therapy of LM in pPTCs(p = 0.003).Conclusion: LM was frequently observed in pPTCs. NMLNs ＞14 was an independent risk factor for LM in our study and other cohorts, and postoperative sTg was a potential predictor for the therapy outcome of LM in pPTCs.

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Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area

European Journal of Nutrition ◽

10.1007/s00394-016-1370-2 ◽

2017 ◽

Vol 57 (2) ◽

pp. 809-815 ◽

Cited By ~ 15

Author(s):

Hye Jeong Kim ◽

Hyeong Kyu Park ◽

Dong Won Byun ◽

Kyoil Suh ◽

Myung Hi Yoo ◽

...

Keyword(s):

Risk Factor ◽

Thyroid Cancer ◽

Cancer Patients ◽

Papillary Thyroid Cancer ◽

Iodine Intake ◽

Papillary Thyroid ◽

Braf Mutations

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A distinctive colour associated with high iodine content in malignant pleural effusion from metastatic papillary thyroid cancer: a case report

Journal of Medical Case Reports ◽

10.1186/1752-1947-7-147 ◽

2013 ◽

Vol 7 (1) ◽

Cited By ~ 8

Author(s):

Andrew Rosenstengel ◽

Ee Mun Lim ◽

Michael Millward ◽

YC Gary Lee

Keyword(s):

Thyroid Cancer ◽

Case Report ◽

Pleural Effusion ◽

Papillary Thyroid Cancer ◽

Malignant Pleural Effusion ◽

Iodine Content ◽

Papillary Thyroid ◽

High Iodine

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Low Urinary Iodine is a Protective Factor of Central Lymph Node Metastasis in Papillary Thyroid Cancer: A Cross-sectional Study

10.21203/rs.3.rs-278269/v1 ◽

2021 ◽

Author(s):

Ziyang Zeng ◽

Kang Li ◽

Xianze Wang ◽

Siwen Ouyang ◽

Zimu Zhang ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Protective Factor ◽

Urinary Iodine ◽

Iodine Intake ◽

Clinicopathological Features ◽

Papillary Thyroid ◽

Central Lymph Node ◽

High Iodine ◽

Central Lymph

Abstract Background: An abrupt increase of thyroid cancer has been witnessed paralleling the supplemented iodine intake in formerly iodine-deficient countries. And increased iodine intake has been linked to the rising incidence rate of papillary thyroid cancer (PTC). However, the correlation between iodine and clinicopathological features of PTC has not been well-characterized. This study aimed to investigate the associations between iodine intake and the clinicopathological features of PTC patients.Methods: 359 PTC patients who have received surgical treatment in Peking Union Medical College Hospital from May 2015 to November 2020 were retrospectively reviewed. The associations between urinary iodine (UI), urinary iodine/creatinine ratio (UI/U-Cr) and the clinicopathological features of PTC were analyzed. Univariate and multivariate analysis were performed to investigate the relationship between UI level and central lymph node metastasis (CLNM).Results: There were no significant differences of UI in different groups according to the variables studied, except that patients with CLNM had higher UI level than CLNM(-) patients. No associations were found between UI/U-Cr and clinicopathological features except variant subtypes (classic/follicular). After dividing patients into high-iodine group and low-iodine group, more patients were found to have CLNM in high-iodine group (p=0.017). In addition, younger age, larger tumor size and classic variant positively correlated with CLNM (p<0.05). Univariate analysis showed that insufficient iodine intake (≤ 99 μg/L) were associated with decreased CLNM risk in PTC. And after defining insufficient iodine intake as ≤ 109 μg/L and above requirements as ≥ 190 μg/L, multivariate analysis showed that lower iodine was associated with CLNM in total population of PTC (OR: 0.53, 95 % CI: 0.31 - 0.91) and in PTC < 1cm (papillary thyroid microcarcinoma, PTMC) (OR: 0.43, 95 % CI: 0.21 - 0.87).Conclusions: Low iodine was a protective factor for CLNM in papillary thyroid cancer, particularly in those < 1 cm. These results indicated that iodine may not only be an initiator of tumorigenesis, but also a promoter of the development of PTC.

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TREM1 fosters an immunosuppressive tumor microenvironment in papillary thyroid cancer

Endocrine Related Cancer ◽

10.1530/erc-21-0297 ◽

2021 ◽

Author(s):

Yang Zhao ◽

Cangang Zhang ◽

Yanan Zhu ◽

Xi Ding ◽

Yikun Zhou ◽

...

Keyword(s):

T Cells ◽

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Molecular Mechanisms ◽

Methylation Status ◽

Disease Free Survival ◽

Papillary Thyroid ◽

Advanced Tumor ◽

Tumor Stages ◽

Immunosuppressive Microenvironment

The immunosuppressive microenvironment is associated with poor prognosis in papillary thyroid cancer (PTC); however, the molecular mechanisms involved are unknown. Among triggering receptor expressed on myeloid cell (TREM) family, we found that TREM1 expression in PTC was significantly higher than that in normal tissues. TREM1 overexpression was associated with BRAFV600E profiles and advanced tumor stages. Furthermore, TREM1 mRNA expression was negatively correlated with promoter methylation status. Specifically, hypomethylation of CpG site cg06196379 in the TREM1 promoter was related with poor patient disease free survival (DFS) and a high PTC recurrence rate. Mechanistically, TREM1 was mainly expressed in malignant epithelial cells but not macrophages in PTC by single-cell analysis. PTC tissues with high TREM1 levels had enhanced infiltration of regulatory T cells (Tregs) and decreased infiltration of CD8+ T cells. Our study confirms that hypomethylation-mediated overexpression of TREM1 in PTC cells promotes an immunosuppressive microenvironment by enhancing Treg infiltration. We recommend the future use of therapeutic strategy targeting TREM1 for the treatment of PTC.

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