Association Of Iodine Intake And BRAF^V600EMutation In Papillary Thyroid Carcinoma

ObjectivesThyroid carcinoma is the most common endocrine malignant tumor. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The incidence of PTC appears to be steadily increasing.BRAFV600E mutation is the most common mutantsite of BRAF gene. There may be associations between the mutation and occurrence, clinical characteristics and treatment of PTC. In the study, we asked whether high iodine intake was a risk factor for the occurrence of BRAF mutation in thyroid gland as a molecular basis for its association with PTC.We hypothesize that there were associations BRAFV600E mutations and clinical biologic characteristics of PTC, and intend to provide scientific basis for reasonable iodine intake and prevention of PTC.MethodsThe patients with PTC were from Tianjin and treated in Tianjin Medical University Cancer Hospital and Institute from August2011to March2012. All information was collected which included epidemiology survey data,medical record,tumor paraffin organization or fresh frozen tissue tumor. A total of159papillary thyroid carcinoma patients and200healthy controls enrolled in this study. Urine samples were collected three times randomly in the first day of admission. We test urine iodine three times and calculate the average. Organization genomic DNA was extracted. A total of200healthy controls enrolled from Tianjin in this study. All information was collected by questionnaire which included demographic data, disease history, family history of cancer, behavior pattern, clinical data laboratory data, pathology and management. All these data were entered into the database and analyzed with SPSS17.0.Results(1) The MUI of the patients and healthy controls is336ug/L and196ug/L respectively.There is a significantly difference about urine iodine value between papillary thyroid carcinoma patients and healthy controls (P=0.004).(2) The overall prevalence of the BRAFV600E mutation in this series of PTC was 63.5%(101of159). The prevalence of the BRAFV600E mutation in this series of PTC with different iodine intake was22.2%,50.0%,62.5%and71.4%respectively.There is a significantly difference about BRAFV600E mutation among groups, showing a clear association of BRAFV600E mutation with iodine intake (P=0.006).(3) we took the advantage of the cases to analyze the relationship of BRAFV600E mutation with clinicopathological characteristics of PTC. There is no association of BRAFV600E mutation with age,gender, tumor size, extrathyroid extension or nodulor goiter in PTC (P>0.05).The analysis showed a significant association of BRAFV600E mutation with lymph nodes metastasis (P=0.008) and Hashimoto’s thyroiditis (P=0.037).(4) To further analyze the relationship between lymph nodes metastasis and BRAFV600E mutation in PTC, we divided the data into four groups according to the levels of urine iodine. There is no significant association of BRAFV600E mutation with cervical lymph nodes metastases in the same group(P=0.167、 P=0.637、P=0.077、P=0.327).(5) To further analyze the relationship between Hashimoto’s thyroiditis and BRAFV600E mutation in PTC, we divided the data into four groups according to the levels of urine iodine. There is no significant association of BRAFV600E mutation with Hashimoto’s thyroiditis in the same group PTC (P=1.000、P=0.637、 P=0.385, P=0.278).Conclusions1. There is a significant difference about urine iodine value between PTC patients and healthy contrals. High iodine intake may be a risk factor of occurrence of papillary thyroid carcinoma.2. In patients of papillary thyroid carcinoma:1) High iodine intake may be a risk factor of BRAFV600E mutation in PTC.2) There is no association of BRAFV600E mutation with age,gender, tumor size, extrathyroid extension or nodulor goiter in PTC3) BRAFV600E mutation in PTC with cervical lymph nodes metastases is more common than PTC without cervical lymph nodes metastases. Among the four groups, iodine intake has no effect on BRAFV600E mutation in the same group patients.4) BRAFV600E mutation in PTC coexisting Hashimoto’s thyroiditis is more uncommon than PTC without Hashimoto’s thyroiditis. Among the four groups, iodine intake has no effect on BRAFV600E mutation in the same group patients.