Association between Serum Level of Multiple Trace Elements and Esophageal Squamous Cell Carcinoma Risk: A Case–Control Study in China

SIMPLE SUMMARY: China accounts for half of the global new cases of esophageal cancer (EC). A disorder of individual trace elements was established as increasing risk for developing esophageal cancer, but the truth was that people are exposed to multiple metals simultaneously in the real world, and research on the relationship between mixtures of accumulative hazards and EC remains scarce. In our current research, we used BKMR, an approach designed to estimate the overall effect of a mixture, to explore the possible role of different trace elements combined in esophageal squamous cell carcinoma (ESCC) risk. In addition, some interesting results were found in our study. We hope it will provide more evidence for environment-related carcinogenesis of ESCC. ABSTRACT: We investigated the associations between multiple serum trace element levels and risk for esophageal squamous cell carcinoma (ESCC). A total of 185 ESCC patients and 191 healthy individuals were recruited in our study. The concentration of 13 trace elements (Al, V, Cr, Mn, Co, Ni, Cu, Zn, As, Se, Sr, Cd and Pb) in serum was determined with inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and the Probit extension of Bayesian Kernel Machine Regression (BKMR) models was established to explore the associations and the cumulative and mixed effects of multiple trace elements on ESCC. Three elements (Zn, Se and Sr) displayed a negative trend with risk for ESCC, and a significant overall effect of the mixture of Al, V, Mn, Ni, Zn, Se and Sr on ESCC was found, with the effects of V, Ni and Sr being nonlinear. Bivariate exposure–response interactions among these trace elements indicated a synergistic effect between Zn and Se, and an impactful difference of V combined with Ni, Sr or Zn. Our results indicate that Ni, V, Al, Mn, Zn, Se and Sr are associated with ESCC risk, providing additional evidence of the complex effects of trace elements disorder during the etiology of EC development.