Abstract 4945: Exposure to per and poly fluoroalkyl substances and cancer risk: A systematic review and meta-analysis
Authors: Monireh Sadat Seyyedsalehi, Paolo Boffetta
Journal: Cancer Research (2025)

Abstract Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that humans can encounter through occupational or environmental exposure. Recent evidence suggests that exposure to PFAS may increase the risk of different types of cancer. In our comprehensive review and meta-analysis, we investigated the association between PFAS exposure and the risks of breast, female genital, bladder, kidney, prostate, testis, liver, esophageal, gastric, colorectal, pancreatic, head and neck, lung, thyroid, and lymphatic cancers. We systematically reviewed literature from IARC Monographs, ATSDR Reports, PubMed, and Scopus (up to January 2024) for cohort, case-control, and ecological studies. Four reviewers independently screened studies, and data extraction included study design, patient characteristics, and effect size measures. The quality of studies was assessed using the modified version of the Newcastle-Ottawa Scale (NOS). We constructed forest plots and random-effects meta-analyses of relative risks (RR) for PFAS-cancer associations with at least 3 independent risk estimates and conducted stratified, dose-response, and publication bias analyses. A total of 41 articles reported results on PFAS exposure and cancer. The pooled RR for the associations between exposure to different types of PFAS and cancer incidence and mortality are reported in Table 1 Table 1: The combined relative risk (RR) of occupational and environmental PFAS exposure and various types of cancer. Cancer type PFAS type RR (95%CI), I2, p value Number of risk estimates Publication bias Breast PFOA 1.08(0.97-1.20), I2=85.2%, p&amp;lt;0.001 21 0.30 PFOS 1.00(0.85-1.18), I2=0.81.5%, p&amp;lt;0.001 12 PFNA 0.95(0.81-1.12), I2=83%, p&amp;lt;0.001 10 PFDA 1.29(0.73- 2.25), I2=91.3%, p&amp;lt;0.001 6 Cervix PFAS overall 0.94(0.79-1.12), I2=0.0%, p=86 3 0.55 PFOA 1.00(0.90-1.11), I2=0.0%, p=0.58 4 Ovary PFAS overall 1.07(1.04-1.09), I2=99.3%, p&amp;lt;0.001 12 PFOA 1.05(0.89-1.24), I2=22.6%, p=0.27 4 Kidney PFAS overall 1.18(1.05-1.32), I2=52.6%, p=0.02 11 0.31 Bladder PFOA 0.93(0.86- 1.01), I2=1%, p=0.43 11 0.79 PFOS 0.94(0.78- 1.13), I2=45.1%, p=0.14 4 Prostate PFOA 0.95(0.91-1.00), I2=34%, p=0.08 17 0.71 PFOS 1.04(0.98-1.11), I2=34.4%, p=0.14 9 PFNA 0.96(0.83-1.12), I2=92.7%, p&amp;lt;0.001 6 Testis PFAS overall 1.12(0.94-1.34), I2=0.0%, p=0.52 8 0.53 Colorectal PFOA 0.83(0.65-1.06), I2=81.6%, p&amp;lt;0.001 6 0.37 PFOS 0.71(0.22-2.27), I2=81.5%, p&amp;lt;0.001 4 Liver PFAS overall 1.03(0.91-1.16), I2=47.9%, p=0.02 16 0.51 Pancreas PFOA 1.01(0.89-1.15), I2=0.0%, p=0.79 9 0.44 Lung PFAS overall 1.20 (1.12-1.28), I2=0.0%, p=0.95 9 0.57 Head and neck PFAS overall 1.15 (0.96-1.37), I2=0.0%, p=0.72 3 0.79 Thyroid PFAS overall 1.54 (0.86-2.78), I2=69.0%, p=0.02 4 0.08 Hodgkin lymphoma PFAS overall 1.23(0.90-1.70), I2=0.0%, p=0.38 3 0.47 Non-Hodgkin lymphoma PFAS overall 1.01(0.90-1.13), I2=31.8%, p=0.19 6 0.64 . Our findings suggest that overall PFAS exposure may be associated with kidney, ovary, and lung cancer and high doses of PFAS with testicular cancer. Further prospective studies with an appropriate assessment of co-exposure with other carcinogens and detailed exposure assessment among study participants are needed to establish causality of observed associations. Citation Format: Monireh Sadat Seyyedsalehi, Paolo Boffetta. Exposure to per and poly fluoroalkyl substances and cancer risk: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4945.