Perfluoroalkyl substances exposure and the risk of breast cancer: A nested case-control study in Jinchang Cohort

Background: As persistent organic pollutants (POPs), perfluoroalkyl substances (PFAS) may potentially impact human health. Our study aimed to investigate the prospective association between PFAS exposure and the incidence risk of breast cancer in females. Methods: By fully following the Jinchang Cohort after a decade, we conducted this nested case-control study with 135 incidence cases of breast cancer (BC) and 540 bias-paired controls. The PFAS levels were tested by baseline serum samples. Conditional logistic regression and a restricted cubic spline model were employed to investigate the BC incidence risks and the dose-response associated with single PFAS component exposure. Furthermore, the Quantile g-computation model (Qgc), random forest model (RFM), and bayesian kernel machine regression models (BKMR) were integrated to estimate the mixed effects of PFAS exposure on the incidence risk of BC. Results: Exposures to specific PFAS components were positively associated with an increased incidence risk of breast cancer. By grouping the study population into different baseline menopausal statuses, PFHxS, PFNA, PFBA, PFUdA, PFOS, and PFDA demonstrated a similarly positive correlation with BC incidence risks. However, the increased incidence risks of BC associated with PFOA, PFOS, PFUdA, and 9CL-PF3ONS exposure were exclusively found in the premenopausal population. Both BKMR and Qgc revealed that exposure to mixed PFAS was associated with an increased risk of breast cancer, with Qgc specifically indicating an odds ratio (OR) of 2.21 (95% CI: 1.53, 3.19). Random forests showed that PFBA, PFOS, PFHxS, and PFDA emerged as predominant factors potentially influencing breast cancer incidence. Conclusion: Our findings suggest a strong association between PFAS exposure and the incidence of breast cancer. Premenopausal women should exercise more caution regarding PFAS exposure.