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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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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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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BRAF mutation assessment in papillary thyroid cancer: are we ready to use it in clinical practice?

Endocrine ◽

10.1007/s12020-013-0139-0 ◽

2013 ◽

Vol 45 (3) ◽

pp. 341-343 ◽

Cited By ~ 19

Author(s):

Efisio Puxeddu ◽

Sebastiano Filetti

Keyword(s):

Thyroid Cancer ◽

Clinical Practice ◽

Papillary Thyroid Cancer ◽

Braf Mutation ◽

Papillary Thyroid

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Urine iodine excretion in patients with papillary thyroid cancer evaluation of the relationship with the presence of BRAF mutation

Journal of Elementology ◽

10.5601/jelem.2020.25.1.1984 ◽

2020 ◽

Author(s):

Mehmet Celik ◽

Sibel Guldiken ◽

Semra Ayturk ◽

Buket Yilmaz Bulbul ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Braf Mutation ◽

Papillary Thyroid ◽

Iodine Excretion ◽

The Relationship ◽

Urine Iodine

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BRAF Mutation Predicts a Poorer Clinical Prognosis for Papillary Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-0987 ◽

2005 ◽

Vol 90 (12) ◽

pp. 6373-6379 ◽

Cited By ~ 627

Author(s):

Mingzhao Xing ◽

William H. Westra ◽

Ralph P. Tufano ◽

Yoram Cohen ◽

Eli Rosenbaum ◽

...

Keyword(s):

Multivariate Analysis ◽

Thyroid Cancer ◽

Risk Stratification ◽

Papillary Thyroid Cancer ◽

Braf Mutation ◽

Advanced Tumor Stage ◽

Papillary Thyroid ◽

Clinical Prognosis ◽

Mutation Status ◽

Predictors Of Recurrence

Context: Use of BRAF mutation in papillary thyroid cancer (PTC) has the potential to improve risk stratification of this cancer. Objective: The objective of the study was to investigate the prognostic value of BRAF mutation in patients with PTC. Design, Setting, and Subjects: In a multicenter study of 219 PTC patients, data on their clinicopathological characteristics and clinical courses between 1990 and 2004 were retrospectively collected, and their tumor BRAF mutation status was determined. Associations of BRAF mutation with initial tumor characteristics and subsequent recurrence were analyzed. Main Outcome Measure: Relationships between the BRAF mutation status and clinicopathological outcomes, including recurrence, were measured. Results: We found a significant association between BRAF mutation and extrathyroidal invasion (P < 0.001), lymph node metastasis (P < 0.001), and advanced tumor stage III/IV (P = 0.007) at initial surgery. This association remained significant on multivariate analysis, adjusting for conventional clinicopathological predictors of recurrence excluding the histological PTC subtype, but was lost when the tumor subtype was included in the model. BRAF mutation was also significantly associated with tumor recurrence, 25 vs. 9% with and without mutation, respectively (P = 0.004), during a median of 15 (interquartile range, 3–29) months of follow-up. This association remained significant on multivariate analysis adjusting for conventional clinicopathological predictors of recurrence, even including the PTC subtype (odds ratio, 4.0; 95% confidence interval, 1.1–14.1; P = 0.03). BRAF mutation was even an independent predictor of recurrence in patients with stage I/II disease, 22 vs. 5% with and without BRAF mutation, respectively (P = 0.002). BRAF mutation was also more frequently associated with absence of tumor I-131 avidity and treatment failure of recurrent disease. Conclusions: In patients with PTC, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence. Therefore, BRAF mutation may be a useful molecular marker to assist in risk stratification for patients with PTC.

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