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

Division of Endocrinology and Metabolism (H.G., M.J., Y.W., P.H., M.X.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Endocrinology and Metabolism and Institute of Endocrinology (H.G., Z.S., W.T.), The First Affiliated Hospital of China Medical University, Shenyang, 110001 Liaoning, the People’s Republic of China; Department of Pathology (R.B.), Chongqing No. 9 People’s Hospital, 400700 Chongqing, the People’s Republic of China; Changzheng Hospital (H.Y.), The Second Military Medical University, 200003 Shanghai, the People’s Republic of China; The Affiliated Hospital of Qingdao University School of Medicine (Y.W.), Qingdao 266003, Shandong, the People’s Republic of China; and Department of Pathology (Y.Z.), China Medical University, Shenyang, 110001 Liaoning, the People’s Republic of China

Address all correspondence and requests for reprints to: Michael Mingzhao Xing, M.D., Ph.D., Division of Endocrinology and Metabolism, the Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21287. E-mail: mxing1{at}jhmi.edu.

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.