Bisphenol A Exposure Associates with Colorectal Cancer Metastasis and Immunosuppression: A Five-Year Cohort Study.

Abstract

Background: Bisphenol A (BPA) is a widespread endocrine-disrupting chemical found in consumer products. While BPA exposure has been associated with various health risks, its specific impact on colorectal cancer (CRC) progression and underlying mechanisms remain poorly understood.

Methods: In this five-year retrospective cohort study, we analyzed 63 CRC patients selected from an initial cohort of 574. Urinary BPA was quantified using HPLC-MS/MS, and patients were stratified into normal (n=15), low (n=30), and high (n=18) BPA exposure groups. Flow cytometry and immunohistochemistry profiled immune cell populations in blood and tumor tissues. Multivariate regression analyses identified relationships between BPA exposure, metabolic parameters, and clinical outcomes.

Results: BPA levels showed significant inverse correlations with HDL/LDL ratio (p=0.010) and positive correlations with BMI (p=0.028). Patients with high BPA exposure demonstrated significantly higher rates of metastasis (61.1% vs. 10% in low exposure and 0% in normal exposure groups, p<0.001) and shorter overall survival (median 20 months vs. 51 months in low exposure group, p=0.034). Flow cytometric analysis revealed dose-dependent reductions in circulating CD8+ T cells, CD4+ T cells, and NK cells with increasing BPA exposure. Immunohistochemical analysis showed pronounced decreases in tumor-infiltrating CD8+ T lymphocytes correlating with BPA exposure levels (p=0.0027). High BPA exposure was also significantly associated with increased post-surgical infection rates (OR=1.9, 95% CI: 1.1-3.1).

Conclusion: These preliminary findings suggest BPA exposure represents a potential risk factor for CRC progression, likely mediated through metabolic alterations and immunosuppression within the tumor microenvironment. Environmental exposures may significantly influence cancer outcomes through immune-metabolic pathways, though further validation in larger cohorts is warranted.