当前碘摄入水平下典型环境污染物联合暴露对甲状腺疾病患病风险的影响

In recent years, the incidence of thyroid disease, such as benign thyroid nodules and thyroid cancer, is on the rise in China. The Universal Salt Iodization has become a matter of great concern. In general, the incidence of thyroid disease was affected by many factors. The role of environmental pollutant substance cannot be ignored. Those pollutants, including Polychlorinated diphenyl dioxin / furan (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenyl dthers (PBDEs), organochlorine pesticides, and perchlorates could disturb the function of thyroid and increase the disease risk. In this study, the impact of human combined exposure to typical environmental pollutants on the risk of thyroid disease with the current dietary intake of iodine would be investigated. 1:4 matched case-control study will be applied in this study. Selected thyroid disease sufferers and matched-healthy individuals will be voluntarily enrolled, and supply some human samples including fasting venous blood and urina sanguinis. The concentration of PCDD/Fs, PCBs, PBDEs, organochlorine pesticides, and perchlorates in selected human samples would be determined, respectively, to represent the human exposure. A survey of food consumption will be conducted to evaluate the dietary intake of iodine. And the level of iodine in the urine would be analyzed to represent individual nutrition status of iodine. Multivariate statistical methods such as logistic regression would be applied to analyze the impact of individual iodine nutritional status, exposure to environmental pollutants and other factors on the risk of thyroid disease, and investigate the contribution of human combined exposure to typical environment pollutants to the incidence of thyroid disease under different nutrition status of iodine. This study will help to scientifically and comprehensively assess the health risk of these pollutants and deeply understand the relationship between iodine and thyroid disease.

近年来我国甲状腺良性结节、甲状腺癌等甲状腺疾病发病率呈上升趋势，全民食盐加碘受到强烈关注甚至质疑。甲状腺疾病受多因素影响，其中环境污染因素不容忽视。二噁英（PCDD/Fs）、多氯联苯（PCBs）、多溴联苯醚（PBDEs）、有机氯农药、高氯酸盐等典型环境污染物具甲状腺干扰作用，可增加患病风险。本研究拟探索当前碘摄入水平下典型环境污染物机体联合暴露对甲状腺疾病患病风险的影响。采用1:4匹配设计病例对照研究，招募特定甲状腺疾病患者并匹配健康对照作为受试人群，采集空腹静脉血和晨尿，测定其中PCDD/Fs、PCBs、PBDEs、有机氯农药、高氯酸盐等含量以表征机体暴露水平。通过膳食调查评价膳食碘摄入水平，并以尿碘水平表征个体碘营养状况。采用logistic回归等统计方法，分析个体碘营养状况、环境污染物机体暴露等多因素对甲状腺疾病发病风险的影响，并考察多种典型环境污染物联合暴露对甲状腺疾病发病贡献。

我国面临较为严重的环境污染问题，甲状腺癌等重大疾病发病率急剧升高。环境因素对甲状腺癌发病风险贡献不容忽视，但缺乏环境污染物暴露与甲状腺癌发病风险的研究数据。本研究按照配对病例对照研究设计，招募116名甲状腺癌患者和116名健康人，收集空腹静脉血和晨尿，以生物样品中高氯酸盐、邻苯二甲酸酯代谢物、双酚A及其替代物的含量，表征机体暴露水平，测定尿中碘含量，表征机体碘营养状况。构建logistic回归模型、多元性线形回归模型和自然样条回归模型等，分析污染物暴露与甲状腺癌发病风险关系并探索机体剂量效应关系。首先，对高氯酸盐和硫氰酸盐与甲状腺癌关系进行了研究。病例组和对照组尿样中碘含量、高氯酸盐含量、硫氰酸盐含量存在显著差别，在条件logistic回归模型中采用逐步后退回归方法，选择合适变量构建最优化模型，最终模型中包含的变量有碘、硫氰酸盐、高氯酸盐和体表面积。碘、高氯酸盐与甲状腺癌发病风险显著性正相关，OR分别为11.01（95%CI：1.97-30.5）和2.27（95%CI：1.03-5.03），而硫氰酸盐则与甲状腺癌发病风险呈显著性负相关，OR为0.24（95%CI：0.09-0.65）。随后，对邻苯二甲酸酯暴露与甲状腺癌关系进行了研究。校正潜在混杂因素（尿碘、尿肌酐、尿高氯酸、尿硫氰酸盐、吸烟、体质指数）后,尿液中DEHP代谢物包括MEHP、MEOHP、MECPP、MEHHP与甲状腺癌正相关，总DEHP代谢物暴露的OR为3.11 (1.49-6.52)，未观察到另外两种邻苯二甲酸酯代谢物MBP和MEP与甲状腺癌发病风险间存在相关性(p>0.05)。DEHP代谢物与甲状腺癌关系不受性别以及碘营养状况的影响。MBP和MEP在较低碘水平下时与甲状腺癌正相关，但较高碘时无统计学意义。最后，考察尿中BPA及其替代物（BPS、BPF、TCBPA）对甲状腺癌发病风险影响，BPF和TCBPA与甲状腺癌正相关，OR分别为1.85（1.14-3.01）和1.41（0.99-2.01），但BPA和BPS则呈现负相关。研究首次揭示多种抗甲状腺物质人体暴露可能造成甲状腺癌发病风险升高，为健康评估和环境管控提供了科学数据。考虑到病例对照设计的固有缺陷和较低的样品量，需要开展较大规模人群的前瞻性队列研究对研究结果进行确认。

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