Examining the relationship between per-and polyfluoroalkyl substances and breast, colorectal, prostate, and ovarian cancers: a meta-analysis

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used widely in industrial and commercial applications. Concerns exist about their potential link to cancer risk as possible endocrine-disrupting chemicals. We conducted a meta-analysis to evaluate the dose-response relationship between PFAS, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluorohexanesulfonic acid (PFHxS) exposure and risk of breast, prostate, colorectal, and ovarian cancers. We systematically searched major databases through May 2022 and identified 13 observational studies for inclusion. Using random-effects models, we calculated summary odds ratios (ORs) and 95% confidence intervals (CIs) comparing the highest versus lowest PFAS exposure categories. Additionally, we analyzed the dose-response correlation between PFAS and cancer risk in a subset of studies. The study revealed no substantial correlation between exposure to PFASs and the incidence of breast cancer (BC) (OR_PFOS = 1.15, 95% CI = 0.91-1.46, OR_PFOA = 1.01, 95% CI = 0.68-1.50, OR_PFNA = 0.88, 95% CI = 0.64-1.21, OR_PFHxS = 1.22, 95% CI = 0.40-3.77, and OR_PFDA = 1.29, 95% CI = 0.41-4.10), ovarian cancer (OR_PFOA = 1.43, 95% CI = 0.84-2.42), prostate cancer (OR_PFOA = 1.05, 95% CI = 0.88-1.26), and colorectal cancer (OR_PFOA = 0.77, 95% CI = 0.53-1.12) in the highest versus lowest exposure analysis. However, dose-response analysis showed that for every 1 ng/ml increase in PFNA and 2 ng/ml increase in PFOA, the relative risk for BC decreased significantly (RR 0.67, 95% CI 0.45-0.99 and RR 0.94, 95% CI 0.89-0.98, respectively). Non-linear dose-response analysis found no significant changes in BC risk with increasing PFAS levels. In conclusion, while the highest versus lowest analysis does not support associations between PFAS exposure and the risk of these cancers, linear dose-response analysis suggests potential inverse relationships between PFNA/PFOA levels and BC risk. Further research is warranted on these potential protective effects.