Objective: To evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case-control cohort.

Methods: We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4’-DDT, and 4,4’-DDE) were measured in the serum by liquid or gas chromatography-mass spectrometry. Unconditional logistic regression, Bayesan Kernel Machine Regression and Weighted Quantile Sum models were used to estimate the association between TC and pollutants’ levels, considered individually or as mixture. BRAFV600E mutation was assessed by standard methods.

Results: The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR= 2.03, 95% CI 1.10-3.75, p=0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR=0.63, 95% CI 0.41-0.98, p=0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of pre-surgical Thyroid-Stimulating Hormone (TSH). PFHxS, PFOS, PFNA and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumours. Statistical models showed a negative association between pollutants’ mixture and TC. BRAFV600E mutations resulted associated with PCB-153, PCB-138 and PCB-180.

Conclusions: Our study suggests, for the first time in a case-control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants’ mixture, likely due to a potential reverse causality.

目的：在意大利病例对照队列中评估一些内分泌干扰性化学物质与甲状腺癌（TC）之间的可能关联。

方法：我们招募了 112 名 TC 患者和 112 名性别和年龄匹配的无已知甲状腺疾病的对照者。通过液相或气相色谱-质谱法测定血清中的全氟烷基物质和多氟烷基物质 (PFAS)、多氯联苯 (PCB) 和二氯二苯基三氯乙烷（4,4'-DDT 和 4,4'-DDE） 。使用无条件逻辑回归、贝叶斯核机器回归和加权分位数和模型来估计 TC 与污染物水平之间的关联（单独考虑或混合考虑）。通过标准方法评估BRAFV600E突变。

结果：全氟癸酸（PFDA）的检测与TC呈正相关（OR=2.03，95%CI 1.10-3.75，p=0.02），而与全氟己磺酸（PFHxS）水平呈负相关（OR=0.63， 95% CI 0.41-0.98，p=0.04）。此外，全氟壬酸（PFNA）与甲状腺炎的存在呈正相关，而全氟辛烷磺酸（PFOS）与术前促甲状腺激素（TSH）水平较高。 PFHxS、PFOS、PFNA 和 PFDA 与侵袭性较小的 TC 相关，而多氯联苯（PCB-105 和 PCB-118）与更大且更具侵袭性的肿瘤相关。统计模型显示污染物混合物与TC之间呈负相关。 BRAFV600E 突变与 PCB-153、PCB-138 和 PCB-180 相关。

结论：我们的研究首次在病例对照人群中表明，接触某些 PFAS 和 PCB 与 TC 以及某些临床和分子特征相关。相反，PFHxS 和污染物混合物均呈负相关，这可能是由于潜在的反向因果关系。