The Relationship Between Iodine Nutrition And The Occurrence/ Development Of Papillary Thyroid Carcinoma

Objective: To investigate the role of iodine nutrition in the development of papillary thyroid carcinoma(PTC)and its underlying mechanisms,and to explore the correlation between iodine nutrition and the incidence of the BRAF T1799 a mutation in papillary thyroid carcinoma.Methods: Methods: 177 samples of PTC patients who underwent total or subtotal thyroidectomy during September 2016 to June 2017 were collected from the affiliated hospital of Qingdao University.The tumor tissues were collected and the genomic DNA was extracted to detect the mutation of BRAF T1799 A via first generation sequencing.The fasting urine specimens were collected and the urine iodine level of these patients was detected.The associated clinical data were collected,either.Additionally,the urine specimens were collected from 168 cases of PTC patients and200 cases of healthy people who had treatment or physical examination in our hospital.Urine iodine quantitative detection were performed and complete clinical data were collected.The thyroid papillary carcinoma lines(TPC-1)and normal thyroid cells(Nthy-ori3-1)were cultured using a 0-80 m M potassium Iodide solution based on the concentration of human blood iodine.We use immunofluorescence technique to detect the degree of DNA damage,and to detect the level of ROS by flow cytometry(h2ax?)to reflect the oxidative stress in cells.0-80 m M potassium Iodide was used to culture the TPC-1 monoclonal cells,and the DNA was extract after 20 weeks to detect BRAF T1799 A gene mutation rate via first-generation of sequencing techniques.The RNA was extracted and differential transcripts were screened by the second-generation sequencing technique.SPSS 23.0,Empower Stats,R Studio and Graph pad Prism6.01 were used for statistical analysis and mapping.Results: With the analysis of clinical data,we found that the urine iodine level of PTC patients was significantly higher than that of nodular goiter and healthy control,and urinary iodine was independent risk factor of PTC occurrence(OR=1.002,p<0.05).PTC Patients with iodine overdose have a significantly larger tumor diameter than normal ones(p=0.046).An inverted U shape relation was found between the level of urine iodine with the tumor diameter,and the turning point is 626mg/l.That is,when urine iodine< 626mg/l,the tumor size was first increased(b=0.0013,p=0.0008),then decreased following the urine iodine level(b=-0.0021,p=0.0334).There were 98 PTC patients with BRAF T1799 A mutation among our study objects,while there were no significant differences in urinary iodine levels between the patients with a positive mutation and those negative ones.First generation sequence to TPC-1 monoclonal cells detected no mutation of the BRAF T1799 A.In vitro assays showed that with the increase of iodine concentration,the degree of DNA damage and oxidative stress level of thyroid cells increased markedly,and the effect of high iodine on papillary carcinoma cell lines was more significant than that of normal thyroid cells.The sequencing analysis of whole transcriptome found a total of 174 differential molecules,and the difference genes were found mainly in the exchange of substance,angiogenesis,damage and repair,cell proliferation and inflammatory reaction according to function enrichment analysis.Pathway analysis shows that differentially expressed genes are mainly related to the p53 pathway,the NOD-like receptor pathway,the TGF? pathway,and so on.Conclusion: High iodine status can also be used as a risk factor for the occurrence and progression of thyroid papillary carcinoma.High iodine can cause oxidative stress reaction of thyroid cells to induce the occurrence of DNA injury.While high iodine status isn't the main mechanism which lead to BRAF T1799 a mutation in thyroid cell.At the same time,high iodine also affects the expression of the RNA level in thyroid cancer cells.