Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
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.
Eur J Nutr. 2018 Mar;57(2):809-815. doi: 10.1007/s00394-016-1370-2. Epub 2017 Mar 3.
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.
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.
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.
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.
碘摄入不足和过量都会导致甲状腺疾病，呈现出 U 型曲线。我们之前的研究表明，在碘充足的韩国，相对较低的[尿碘浓度（UIC）<300μg/L]和极高的（UIC≥2500μg/L）碘摄入与甲状腺癌有关。甲状腺乳头状癌（PTC）占甲状腺癌的 97%以上，韩国 80%或更多的 PTC 病例携带 BRAF 突变。我们旨在探讨碘摄入与韩国 PTC 中 BRAF 突变发生率之间的关系。
通过电感耦合等离子体质谱法测量 UIC。通过等位基因特异性聚合酶链反应和 3'-修饰寡核苷酸测序的突变富集来检测 BRAF 突变。使用多变量逻辑回归模型评估 PTC 中 BRAF 突变发生的危险因素。
所有 PTC 患者的中位 UIC 为 287μg/L（范围为 7 至 7426μg/L）。根据世界卫生组织碘建议，近一半的患者（102/215，47%）属于碘摄入过多的类别（UIC≥300μg/L）。在 UIC 为 300-499μg/L 的组中，BRAF 突变的频率最低；与相对较低（UIC<300μg/L）和碘摄入过多（UIC≥500μg/L）的组相比，差异有统计学意义。UIC 是 PTC 中 BRAF 突变的独立预测因子。在多变量调整的比值比（95%置信区间）中，相对低碘摄入组和碘摄入过多组 BRAF 突变的比值比分别为 4.761（1.764-12.850）和 6.240（2.080-18.726），与 300-499μg/L UIC 组相比。
相对低碘摄入和碘摄入过多似乎是甲状腺 BRAF 突变发生的显著危险因素，因此可能是碘充足地区 PTC 发生的危险因素。
