Per- and polyfluoroalkyl substances and the risk of thyroid and breast cancer: Evidence from a meta-analysis and computational toxicology.
Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants with endocrine-disrupting and carcinogenic effects, but epidemiological evidence linking PFAS exposure to cancer remains inconsistent. We conducted a meta-analysis to systematically evaluate associations between PFAS exposure and risks of thyroid and breast cancer. Relevant literature published between January 2003 and May 2025 was retrieved from Web of Science and PubMed. The analysis showed that the pooled odds ratios (ORs) for perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) in relation to thyroid cancer were 0.87 (95% CI: 0.77-0.98) and 0.84 (95% CI: 0.75-0.94), respectively. In contrast, the pooled OR for overall PFAS exposure and breast cancer was 1.04 (95% CI: 1.00-1.09, I2 = 62.2%), indicating no statistically significant association but suggesting a borderline trend. Notably, PFAS exposure was inversely associated with invasive breast cancer (OR = 0.45, 95% CI: 0.26-0.76). Computational toxicology analyses indicated that PFAS may interact with endocrine- and growth factor-related pathways involving EGFR, AKT1, and ESR1, providing supportive but hypothesis-generating mechanistic context. This study highlights specific PFAS compounds that may be associated with altered risks of thyroid and breast cancer. Future high-quality prospective studies with standardized exposure assessments are warranted to clarify the potential carcinogenic effects of PFAS.