Environment International
Metabolomics insights into the association between organochlorine pesticides, synthetic pyrethroids exposure and thyroid cancer risk
By Fei Wang, Chunxiang Li, Linfang Zou and 7 others.
Abstract
Background
The association between organochlorine pesticides (OCPs)/synthetic pyrethroids (SPs) and thyroid cancer (TC) remains poorly understood, with metabolic mechanisms unexplored.
Methods
We conducted a 1:1 age- and sex-matched case–control study (n = 668). Serum levels of 27 target analytes (19 OCPs and 8 SPs) were quantified; subsequent analyses were restricted to 13 compounds (10 OCPs and 3 SPs) with detection frequencies ≥85%. Eight machine learning (ML) algorithms with Shapley Additive Explanations (SHAP) were used to identify key pollutants in the 334 case-control pairs. Untargeted metabolomics was performed in a subset of 50 age- and sex-matched case-control pairs. Mixture effects were assessed by Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression. Furthermore, the Latent Unknown Clustering Integrating Multi-Omics Data (LUCID) model was employed to integrate exposure and metabolic data, enabling the identification of TC patient subgroups and the exploration of underlying metabolic mechanisms.
