浙江大学学报（医学版）2026，Vol.55Issue(6)：551-560,10.DOI:10.3724/zdxbyxb-2025-0645
金属元素混合暴露与甲状腺癌发病风险的关联研究
Association between mixed metal element exposure and the risk of thyroid carcinoma:a case-control study
摘要
Abstract
Objective:To investigate the association between urinary metal element concentrations and the risk of papillary thyroid carcinoma(PTC),to identify key risk factors,and to evaluate the combined effects and interactions of metal element exposure.Methods:A 1∶1 matched case-control study was adopted,including 189 pairs of newly diagnosed PTC patients and healthy controls matched by age and sex.Urinary concentrations of metal elements were measured using inductively coupled plasma mass spectrometry.Conditional logistic regression was applied to evaluate the associations of individual and mixed metal element exposure with PTC risk.Least absolute shrinkage and selection operator(LASSO)regression was used to screen for key metal elements.Weighted quantile sum(WQS)regression was employed to identify the main contributors to the mixture effect.Finally,a Bayesian kernel machine regression(BKMR)model was constructed to assess the overall effect of mixed metal element exposure and potential interactions among metal elements.Results:Multivariable conditional logistic regression showed that,in the model adjusted for multiple metal elements,elevated urinary concentra-tions of nickel,molybdenum,and barium were associated with an increased risk of thyroid carcinoma,with ORs(95%CIs)of 2.08(1.53-2.96),2.78(1.68-4.77),and 2.42(1.80-3.33),respectively;selenium and copper were negatively associated with thyroid carcinoma risk,with ORs(95%CIs)of 0.20(0.15-0.37)and 0.31(0.16-0.60),respectively.LASSO regression identified eight metal elements as key predictors:chromium,nickel,selenium,molybdenum,lead,iron,copper,and barium.WQS regression showed that nickel,barium,and molybdenum had relatively high weights in the positive constraint model,while copper and selenium had relatively high weights in the negative constraint model,suggesting that these metal elements may be major contributors to the overall mixture effect.The BKMR model indicated a nonlinear association between mixed metal element exposure and thyroid carcinoma risk,with potential effect modification among metal elements.Conclusions:Nickel,molybdenum,and barium exposure may be risk factors for thyroid carcinoma,copper may have a protective effect,while association between selenium and thyroid carcinoma risk showed an inverted U-shaped pattern.The effect of mixed metal element exposure was characterized by non-linearity and concentration dependence,with potential interactions among different metal elements.关键词
甲状腺癌/金属元素/暴露评估/混合效应/风险因子Key words
Thyroid carcinoma/Metal element/Exposure assessment/Mixture effect/Risk factor分类
医药卫生引用本文复制引用
湛梓剑,马帅,曾晓鹏,叶敏,刘思涵,宋嘉宜,张建清..金属元素混合暴露与甲状腺癌发病风险的关联研究[J].浙江大学学报（医学版）,2026,55(6):551-560,10.基金项目
国家自然科学基金(22176132) （22176132）
深圳市医学研究专项(B2403008)The study was supported by National Natural Science Foundation of China(22176132)and Shenzhen Medical Research Fund(B2403008) （B2403008）
