Abstract

Alterations in heavy metals and trace element levels may be associated with various cancers. However, the role of this interaction in colorectal cancer (CRC) progression is unclear. In recent years, Principal Component Analysis (PCA) and Bayesian Kernel Machine Regression (BKMR) models have provided new ideas for analyzing the effects of metal mixtures on CRC progression. Herein, we assessed the differences in the levels of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), nickel (Ni), selenium (Se), and zinc (Zn) in tumors and adjacent healthy tissues, to investigate the relationship between heavy metals/trace elements and CRC progression. Surgical samples of CRC and noncancerous tissues were collected, and trace metal levels were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression, PCA, and BKMR models were used to investigate the relationship between heavy metals and trace elements and the degree of tumor differentiation and lymph node metastasis in CRC. Cancer tissues showed lower As, Cd, Co, and Cr concentrations, and higher Se concentrations than healthy tissues (P < 0.05). In addition, CRC patients with poorly differentiated tumors and/or positive lymph node metastases had lower levels of Cd, Zn, Cu, and Se (P < 0.05). Logistic regression showed that single metal concentration was negatively correlated with CRC progression. PCA and BKMR models also showed that the metal mixture concentration was negatively correlated with CRC progression, with Cd contributing the most. Overall, changes in heavy metal and trace element levels may be related to the development of CRC; however, further mechanistic studies are required.

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