Plasma chlorinated paraffin mixtures and breast cancer: Nonlinear patterns in an exploratory case-control study

Increasing evidence suggests that chlorinated paraffins (CPs) exhibit estrogen-disrupting effects, thus necessitating further investigation into their impact on breast cancer development. Building upon this context, we analyzed plasma samples from 70 clinically diagnosed breast cancer patients and 101 healthy controls recruited from screening programs, aiming to quantitatively assess their internal CPs exposure levels. The results showed that short-chain chlorinated paraffins were detected in all plasma samples, with a detection rate of 100.0% and a concentration of 9.58 (4.09, 15.71) ng/mL. Medium-chain chlorinated paraffins had a detection rate of 90.1% and a concentration of 14.40 (7.83, 23.76) ng/mL. The median concentration of SCCPs were lower in the case group than in controls (6.75 vs. 11.42 ng/mL, P < 0.01), whereas MCCPs levels showed no significant difference (14.35 vs. 14.48 ng/mL, P = 0.485). Using the Bayesian kernel machine regression model, we observed an association between mixed CPs exposure and breast cancer risk-driven by C₁₃H₂₃C_l5-SCCPs and C₁₆H₂₇C_l7-MCCPs-which was evident only when all mixture components were jointly fixed at the upper exposure percentiles relative to their median levels. Further exploratory stratified analysis suggests potential associations between CPs exposure and the luminal A and luminal B subtypes of breast cancer, with C₁₆H₂₇Cl₇-MCCPs may potentially contribute to the development of the Luminal A subtype. Molecular docking suggested the potential for interactions between selected CP congeners and estrogen receptors. As an exploratory case-control study, we found that exposure to higher concentrations of CP mixtures may be associated with breast cancer case status, providing evidence for understanding the potential health risks of CPs based on a small-sample population, and also laying the foundation for subsequent mechanistic studies and environmental health risk assessments. However, due to the limited sample size, these findings need to be confirmed in larger-scale prospective studies.