ObjectiveTo 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 multiple metal elements exposure.MethodsA 1∶1 matched case-control study design was adopted, including 189 pairs of newly diagnosed PTC patients and healthy controls matched by age(±5 years) and sex. Urinary concentrations of 13 metal elements were measured using inductively coupled plasma mass spectrometry. Conditional logistic regression was applied to evaluate the associations of individual and mixed metal elements 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 metal elements mixture exposure and potential interactions among metal elements.ResultsMultivariable conditional logistic regression showed that, in the model adjusted for multiple metal elements, elevated urinary concentrations of nickel, molybdenum, and barium were associated with an increased risk of thyroid cancer, 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 cancer 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, molybdenum, and barium 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 metal elements mixture exposure and thyroid cancer risk. Single-metal element exposure-response analyses suggested that increased exposure levels of nickel and barium were associated with increased thyroid cancer risk, whereas increased copper exposure was associated with reduced risk; molybdenum showed an increasing risk trend at high exposure levels, and selenium exhibited an inverted U-shaped pattern. Bivariate exposure-response functions showed that the slopes and trends of some metal element combinations varied across fixed percentiles, suggesting potential effect modification among metal elements.ConclusionsUrinary exposure to nickel, molybdenum, and barium may be risk factors for thyroid cancer, while copper may have a protective effect. The association between selenium and thyroid cancer risk showed a nonlinear pattern. The effect of multi-metal elements mixture exposure was characterized by non-linearity and concentration dependence, suggesting that metal elements co-exposure and potential effect modification should be considered in environmental risk assessment for thyroid cancer.
Zhan et al. (Mon,) studied this question.