title: Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area.
abstract: OBJECTIVE
  Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC) <300 μg/L] and extremely excessive (UIC ≥ 2500 μg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea.
  
  
  METHODS
  UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models.
  
  
  RESULTS
  The median UIC in all patients with PTC was 287 μg/L (range from 7 to 7, 426 μg/L). Nearly half of the patients (102/215, 47%) belonged to the excessive iodine intake category (UIC ≥ 300 μg/L) according to the WHO iodine recommendations. The frequency of BRAF mutations was lowest in the 300-499 μg/L UIC group; it was significantly different compared to the relatively low (UIC < 300 μg/L) and more than excessive (UIC ≥ 500 μg/L) iodine intake groups. UIC was an independent predictor for BRAF mutations in PTC. The multivariate-adjusted odds ratios (95% confidence intervals) in the relatively low and more than excessive iodine intake groups for the BRAF mutation were 4.761 (1.764-12.850) and 6.240 (2.080-18.726), respectively, compared to the 300-499 μg/L UIC group.
  
  
  CONCLUSIONS
  Relatively low iodine intake and more than excessive iodine intake seem to be significant risk factors for the occurrence of BRAF mutations in the thyroid and, therefore, may be risk factors for the development of PTC in an iodine-replete area.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyeong Kyu
authors.initials: HK
authors.lastname: Park
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Byun
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyoil
authors.initials: K
authors.lastname: Suh
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Myung Hi
authors.initials: MH
authors.lastname: Yoo
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea.
authors.forename: Yong-Ki
authors.initials: YK
authors.lastname: Min
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea.
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, #81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea. thyroid@skku.edu.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Chung
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003677:Deficiency Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000652:urine; D004032:Diet / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D019456:Health Transition; D006801:Humans; D015994:Incidence; D007455:Iodine / Q000172:deficiency / Q000506:poisoning* / Q000652:urine; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D054647:Nutrigenomics / Q000379:methods; D009752:Nutritional Status; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D066106:Seoul / Q000453:epidemiology; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D007455:Iodine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF mutation; Iodine; Papillary thyroid cancer