Second, this study also found that the levels of TSH and Tg were associated with thyroid cancer risk only among smokers. with TPOAb levels above 30?IU/mL (OR = 8.47, 95% CI = 5.39?-?13.33 for 30C60?IU/mL and OR = 4.48, 95% CI = 2.59?-?7.76 for 60?IU/mL). Stratified analyses indicated that some of these associations differed by sex, BMI, smoking status, and the duration of follow-up. Conclusions This study demonstrated that the levels of biomarkers of thyroid function/autoimmunity, particularly the presence of TPOAb, might be used as diagnostic markers for predicting thyroid cancer risk. Our findings suggest that careful monitoring of thyroid biomarkers may be helpful for identifying Korean populations at high-risk for thyroid cancer. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-873) contains supplementary material, which is available to authorized users. = 0.019); however, no differences with respect to other variables were observed between the cases and controls. Table 1 General characteristics of the study subjects <0.05. The associations of some markers with thyroid cancer risk appeared to be different when the data were stratified by sex, BMI, smoking status, or the duration of follow-up (Table?3). The association between FT4 levels and thyroid cancer risk was only significant among women or those with a BMI <23?kg/m2. The elevated risk for the middle tertile Pergolide Mesylate of TSH was only significant among men, those with a BMI 23?kg/m2, or former/current smokers. The levels of TT3, FT4, and TSH were associated with Pergolide Mesylate thyroid cancer risk only when the duration of follow-up was shorter than 3?years. However, in all of the analyses, the presence of TPOAb strongly elevated the risk of thyroid cancer. Additionally, we examined whether other known risk factors showed different distributions according to the presence of TPOAb, but no differences were observed (Additional file 1: Table S1). Table 3 The association between thyroid function/autoimmunity Pergolide Mesylate biomarkers and thyroid cancer risk, stratified by sex, BMI, smoking status, and the duration of follow-up a <0.05. Finally, we examined the role of TPOAb in the association between the other biomarkers (TT3, FT4, TSH, Tg, and TgAb) and thyroid cancer risk (Table?4). The association between FT4 and thyroid cancer risk was stronger among those with TPOAb levels <30?IU/mL (OR = 2.12, 95% CI = 1.06?-?4.24). Table 4 The association between thyroid function/autoimmunity biomarkers and thyroid cancer risk, stratified by the presence of TPOAb <0.05. Discussion This study prospectively investigated the association between biomarkers of Pergolide Mesylate thyroid function/autoimmunity and thyroid cancer risk and found that differences in the levels of thyroid biomarkers, particularly TPOAb, could predict the incidence of thyroid cancer. Several studies have examined the association between thyroid function and thyroid cancer risk [6C8, 16, 17]. A large population-based cohort study from Taiwan [8] has investigated the incidence of cancer in patients with hyperthyroidism and found that patients with hyperthyroidism were at an increased risk for thyroid cancer. This group also reported that the Pergolide Mesylate duration of hyperthyroidism was related to increased risk of thyroid cancer. In the present study, the levels of thyroid hormones were normal in most of the study participants. However, relatively higher levels of FT4 showed a positive association with thyroid cancer risk. Because the association between thyroid hormones and thyroid cancer risk has not been sufficiently studied, the underlying mechanisms still remain unclear. Pellegriti reported that circulating TSH receptor-stimulating antibodies (TSHR-Abs) were present in all patients with Graves disease [18], implying an association between TSHR-Abs and elevated levels of thyroid hormones. TSHR-Abs are known to FGF5 stimulate the same intracellular signal pathways as TSH, which has mitogenic and antiapoptotic effects on thyroid follicular cells and thus may play a role in thyroid cancer initiation [19]. The positive association between TSH levels and thyroid cancer risk has been reported in some studies [6, 7, 16, 17], implying that high TSH levels may play a key role in the initiation of thyroid carcinogenesis. TSH has a proliferative effect on thyroid cell growth.