Per-And Poly-Fluoroalkyl Substances (PFAS) Exposure and Risk of Breast, and Female Genital Cancers - A Systematic Review and Meta-Analysis

Sep 21, 2026

PFAS are synthetic chemicals encountered through occupational or environmental exposure, and they may interfere with endocrine and hormonal functions. This systematic review and meta-analysis evaluates links between PFAS exposure and breast and female genital cancers. Literature from IARC Monographs, ATSDR documents, and PubMed (to January 2024) is reviewed across cohort, case-control, and ecological designs, with quality assessed using a modified Newcastle-Ottawa Scale.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages31

Reading Time1 h 18 min

AccessFree to download

Background

Methods

Study selection and data extraction

Quality assessment and statistical approach

Results

Breast cancer findings

Ovarian cancer findings

Heterogeneity and bias evaluation

Conclusion

Reviews, commentaries, perspectives Med. Lav. 2024; 115 (6): e2024043 DOI: 10.23749/mdl.v115i6 .16330 Per-And Poly-Fluoroalkyl Substances (PFAS) Exposure and Risk of Breast, and Female Genital Cancers: A Systematic Review and Meta-Analysis Monireh Sadat Seyyedsalehi1, Elizabeth Maria Kappil2, Sirui Zhang2, Tongzhang Zheng2, Paolo Boffetta1,3,4,* 1Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy 2Brown University School of Public Health, Providence, RI, USA 3Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA 4Department of Family, Population and Preventive Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA Keywords: Breast; Occupational Factors; Endometrial; Female Genital; Malignant; Endocrine Gland; Hormone; Perfluorooctanoic Acid; PFAS; Perfluorooctane Sulfonic Acid AbstrAct Background: PFASs, synthetic chemicals, can be encountered by humans through occupational or environmental exposure, and some reports suggest that they can disrupt endocrine and hormonal activities. In this comprehensive review and meta-analysis, we explored the connection between exposure to PFASs and the risks of breast andfemale genital cancers. Methods: We systematically reviewed the literaturefrom IARC Monographs, ATSDR documents, and PubMed (as of January 2024) for cohort, case-control, and ecological studies on PFAS exposure and breast or female genital cancers. 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). Forest plots of relative risks (RR) were constructedfor breast andfemale genital cancer.Meta-analyses were conducted using random-effects models,stratified analyses,dose-response assessments,and publication bias evaluation. Results: The meta-analysis included 24 studies, comprising 10 cohort, 13 case-control, and one ecological study. The summary relative risk (RR) of breast cancer for PFOA exposure was 1.08 (95% CI = 0.97-1.20; n=21), andfor PFOS was 1.00 (95% CI = 0.85-1.18; n=12). The RR for ovarian cancer and PFAS was 1.07 (95% CI = 1.04-1.09; n=12). The stratification by quality score, year of publication, and exposure source did not reveal any differences. However, analysis by geographical region (p=0.01) and study design (p=0.03) did show differences, particularly in terms of incidence. Stratified analyses of the dose-response relationship did not reveal a trend in the risk of breast cancer orfemale genital cancers, and no publication bias was found for either cancer type. No results were available for cervical and endometrial cancers. Conclusion: In summary, our results suggest an association between PFAS exposure and ovarian cancer and a possible effect on breast cancer incidence in some specific groups. However, bias and confounding cannot be excluded and prevent conclusions regarding causality. Received 25.08.2024 – Accepted 11.11.2024 *Corresponding Author: Paolo Boffetta; E-mail: paolo.boffetta@unibo.it 2 Seyyedsalehi et al Abbreviations: - Agency for Toxic Substances and Disease Registry; ATSDR - The Environmental Protection Agency; EPA - The European Chemicals Agency; ECHA - Endocrine-disrupting chemicals; EDCs - Human papillomavirus; HPV - The International Agency for Research on Cancer; IARC - Nitrogen dioxide; NO2 - Odds ratio; OR - Risk ratio, rate ratio; RR - Standardized mortality ratio; SMR - Standardized incidence ratio; SIR - Perfluorooctanoic Acid; PFOA - Per-and poly-fluoroalkyl substances; PFAS - Perfluorooctane sulfonic acid; PFOS - Perfluorononanoic acid; PFNA - Perfluorobutane sulfonate; PFBS - Perfluorohexanesulfonic acid; PFHxS 1. IntroductIon Breast cancer (BC) is the most commonly diagnosed cancer (ASR=46.8 per 100,000) and the leading cause of cancer death (ASMR=12.7 p

FAQs

What is the main research question of this review?

The review examines whether exposure to PFAS is associated with the risks of breast and female genital cancers, using evidence from multiple study designs.

How were studies selected and analyzed?

Studies were systematically searched in IARC Monographs, ATSDR documents, and PubMed (up to January 2024). Four reviewers screened studies independently, extracted design and patient characteristics plus effect sizes, assessed quality with a modified Newcastle-Ottawa Scale, and used forest plots and random-effects meta-analyses.

What did the meta-analysis find about breast and ovarian cancer risks?

For breast cancer, summary relative risks for PFOA and PFOS were close to 1, with confidence intervals spanning values compatible with no clear association. For ovarian cancer, the relative risk associated with PFAS exposure was 1.07 (95% CI 1.04–1.09), suggesting an association, while dose-response analyses showed no trend.

Sep 21, 2026

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