Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies

Michael B. Zimmermann, Valeria Galetti

Thyroid cancer (TC) is the most common endocrine malignancy and in most countries, incidence rates are increasing. Although differences in population iodine intake are a determinant of benign thyroid disorders, the role of iodine intake in TC remains uncertain. We review the evidence linking iodine intake and TC from animal studies, ecological studies of iodine intake and differentiated and undifferentiated TC, iodine intake and mortality from TC and occult TC at autopsy, as well as the case-control and cohort studies of TC and intake of seafood and milk products. We perform a new meta-analysis of pooled measures of effect from case-control studies of total iodine intake and TC. Finally, we examine the post-Chernobyl studies linking iodine status and risk of TC after radiation exposure. The available evidence suggests iodine deficiency is a risk factor for TC, particularly for follicular TC and possibly, for anaplastic TC. This conclusion is based on: a) consistent data showing an increase in TC (mainly follicular) in iodine deficient animals; b) a plausible mechanism (chronic TSH stimulation induced by iodine deficiency); c) consistent data from before and after studies of iodine prophylaxis showing a decrease in follicular TC and anaplastic TC; d) the indirect association between changes in iodine intake and TC mortality in the decade from 2000 to 2010; e) the autopsy studies of occult TC showing higher microcarcinoma rates with lower iodine intakes; and f) the case control studies suggesting lower risk of TC with higher total iodine intakes.