Association between excessive chronic iodine exposure and the occurrence of papillary thyroid carcinoma

Huang, Fengyan; Zhou, Yong; Gong, Maosong; Sun, Jingfu; Shan, Liqun; Xiao, Qiang; Wang, Lihua; Liu, Jianing; Yu, Zhengping; Jia, Hongying

doi:10.3892/ol.2020.12051

Cited by 7 publications

(14 citation statements)

References 32 publications

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“…According to UIC, more than half of those with PTC exhibited excessive iodine concentrations (i.e., >300 μg/L). This finding is in agreement with previous studies, which showed an excessive UIC in 67.0% of patients with PTC compared to 19.9% in the control group [22] or in 44.3% of patients with PTC compared to 22.2% of patients without PTC [23]. A case-control study in China reported the median UIC was 517.2 μg/L in PTC patients compared to 194.3 μg/L in a control group [24], and another study in Korea reported a level of 786.0 μg/L in PTC patients compared to 112.0 μg/L in a control group [25].…”

Section: Discussionsupporting

confidence: 94%

Evaluation of Iodine Status among Korean Patients with Papillary Thyroid Cancer Using Dietary and Urinary Iodine

2021

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Background: Concerns have been raised regarding thyroid disorders caused by excessive iodine in Koreans, who have iodine-rich diets. This study evaluated iodine status using dietary iodine intake and urinary iodine in papillary thyroid cancer (PTC) patients. Methods: Dietary data of PTC patients were assessed using a 24-hour recall and food frequency questionnaire (FFQ), and urinary iodine concentrations (UICs) were also obtained. To compare the iodine status of PTC patients, Korean adults with or without thyroid disease from the Korea National Health and Nutrition Examination Survey, which had 24-hour recall data and urinary iodine measurements, were analyzed. Results: The median daily iodine intake by 24-hour recall was 341.7 μg/day in PTC patients, similar to the levels of other Korean adults. Based on UICs, the prevalence of excessive iodine was 54.4% in PTC patients, which was similar to the prevalence among subjects with thyroid disease (55.4%) but slightly higher than that in subjects without thyroid disease (47.7%). Based on dietary iodine by 24-hour recall, the prevalence of excessive iodine intake was 7.2%, which was higher than that among subjects with (4.4%) or without (3.9%) thyroid disease. The dietary iodine intake based on 24-hour recall was closely correlated with the UIC (r=0.4826) in PTC patients, but dietary iodine by FFQ was not significantly correlated with either 24-hour recall or UIC-based dietary iodine. Conclusion: Excessive iodine intake was more common in PTC patients than in subjects without thyroid disease. Further longitudinal research is necessary to elucidate the role of dietary iodine in PTC.

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Section: Discussionsupporting

confidence: 94%

Evaluation of Iodine Status among Korean Patients with Papillary Thyroid Cancer Using Dietary and Urinary Iodine

2021

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“…Furthermore, previous study demonstrated that high iodine stimulation (supplemented dose, 7.3 mg/L) can markedly perturb the mRNA and protein expression of SLC transporters (SLC5A5 and SLC26A4) in thyroid tissues of Wistar rats, in comparison to control group 25 . Combined with the results of our previous research that high iodine closely associated with the risk of capsule invasion and thyroid metastasis of PTCs 19 . Therefore, these data together supported a speculation that excess iodine intakes might through up-regulated of SLC34A2 and down-regulated of SLC4A4, contributed to capsule invasion and extra-thyroid metastasis of PTCs.…”

Section: Discussionsupporting

confidence: 68%

“…The methods of urinary iodine concentration (UIC) detection and quality controls, as well as the water iodine assessment were the same as our previously study 19 . According to the recommendations of the World Health Organization, the iodine nutritional status of individual's was categorized into three degrees as follows: i) low UIC (<100 ug/l), iodine-deficient; ii) adaptive UIC (100-299 ug/l), iodine-adequate; and iii) high UIC (≥300 ug/l), iodine-excessive.…”

Section: Methodsmentioning

confidence: 99%

SLC34A2 Up-regulation And SLC4A4 Down-regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas

Huang¹,

Wang²,

Shao³

et al. 2021

J. Cancer

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Papillary thyroid carcinoma (PTC) is one of the fastest growing endocrine system malignant carcinomas detected over the past decade. Unfortunately, more than 25% of PTC patients are characterized by their aggressiveness and subsequent metastasis; these characteristics usually indicate poor prognosis. Recently, increasing evidence has suggested that solute carrier (SLC) transporters may play a pivotal role in the initiation, invasion and metastasis of human carcinoma. However, the expression and clinicopathological significance of SLC transporters in patients with PTC remains undetermined. In this study, we aimed to elucidate how the differential expression of SLC transporters affects clinicopathological features, as well as determine the possible regulatory signaling pathways involved. Three differentially expressed SLC transporters were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database using a bioinformatics approach. The results indicated that high SLC34A2 and low SLC4A4 protein expression exhibited a higher percentage of capsular invasion and extra-thyroid metastasis in patients. Logistic regression analysis showed that high SLC34A2 expression in tumors was identified as an independent risk factor for capsular invasion [odds ratio (OR)=11.400, 95% confidence interval (CI)=1.733-74.995, P=0.011] and extra-thyroid metastasis (OR=4.920, 95%CI=1.234-19.623, P=0.024), while low SLC4A4 expression in tumors was only identified as independent risk factors for extra-thyroid metastasis (OR=8.568, 95%CI =1.186-61.906, P=0.033). Specifically, for tumors with capsular invasion and extra-thyroid metastasis, the protein expression staining of SLC34A2 was markedly enhanced in the cytoplasm of follicular epithelial cells, contrastingly, SLC4A4 expression was notably weakened in the cytomembrane and nucleus. Intriguingly, both high SLC34A2 and low SLC4A4 protein expression were significantly linked to a high urinary iodine concentration in patients with PTC. Mechanistically, compared with adjacent normal thyroids, p-ERK was significantly up-regulated by 17.8% in the invading tumor; p-ERK, p-JNK, and p-P38 were markedly up-regulated by 29.2%, 67.1%, and 38.9% for metastatic tumors, respectively. Importantly, SLC4A4 negatively correlated with p-JNK (r=-0.696, P= 0.004) and p-P38 (r=-0.534, P=0.049). In conclusion, we suggest that up-regulated SLC34A2 (mainly in the cytoplasm) and down-regulated SLC4A4 (mainly in the cytomembrane and nucleus), which might be attributed to excess iodine intake, were closely linked to extra-thyroid metastasis in PTCs. Furthermore, this effect of SLC4A4 may be through the activation of JNK/P38 MAPK signaling pathway. Future in vivo and in vitro gain-or loss-of-function experiments are needed to verify these findings and further elucidate the deeper molecular mechanisms.

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“…In one study the PTC risk associated with an excessive UIC did not differ significantly between cases and controls [ 28 ]. In addition, four studies used patients with thyroid nodules as the control group and may have underestimated the effect of UIC on the risk of PTC because iodine and thyroid hormones are involved in thyroid growth and differentiation [ 28 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…As in our study, some previous studies have reported the effect of excessive UIC on the clinicopathological aggressiveness of PTC, but their results were inconsistent. Some studies found a relationship between excessive iodine intake and an increased risk of lymph node metastasis [ 30 ], larger tumor size [ 32 ], capsular invasion [ 31 , 32 ], bilateral location [ 30 ], extra-thyroid metastasis [ 31 ] and BRAF V600E or T17799A mutation [ 33 , 34 ], while other studies have not found an association between excessive iodine intake and lymph node metastasis [ 31 , 32 ], tumor size [ 31 , 33 ], multifocal tumors or bilaterality [ 31 , 32 ], extracapsular extension [ 32 ] or BRAF mutations [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study

et al. 2021

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Background: This study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC).Methods: A case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression.Results: Excessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels.Conclusion: Excessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

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Association between excessive chronic iodine exposure and the occurrence of papillary thyroid carcinoma

Cited by 7 publications

References 32 publications

Evaluation of Iodine Status among Korean Patients with Papillary Thyroid Cancer Using Dietary and Urinary Iodine

Evaluation of Iodine Status among Korean Patients with Papillary Thyroid Cancer Using Dietary and Urinary Iodine

SLC34A2 Up-regulation And SLC4A4 Down-regulation Correlates With Invasion, Metastasis, And The MAPK Signaling Pathway In Papillary Thyroid Carcinomas

Association between Iodine Intake, Thyroid Function, and Papillary Thyroid Cancer: A Case-Control Study

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