Per- and poly-fluoroalkyl substances exposure and risk of gastrointestinal cancers: A systematic review and meta-analysis

Background Per- and poly-fluoroalkyl substances (PFASs) are a group of synthetic chemicals used since the 1940s in industrial and consumer applications. These substances are known or suspected to cause cancer, particularly kidney and testicular cancer. However, their association with other types of cancer is not well understood. This review aims to investigate the link between PFAS exposure and the risks of other cancers, including gastrointestinal cancers such as esophageal, gastric, colorectal, and pancreatic cancer. Methods We conducted a systematic review of literature from the International Agency for Research on Cancer Monographs, Agency for Toxic Substances and Disease Registry documents, and PubMed (up to January 2024) focusing on the association between PFAS exposure and gastrointestinal cancers. Four independent reviewers screened the studies, extracted the information, and evaluated the quality of the studies using a modified Newcastle-Ottawa Scale. Meta-analyses were performed with random-effects models, including stratified analyses and dose-response assessments. Results The meta-analysis included 17 studies. The summary relative risks (RR) of esophageal cancer for perfluorooctanoic acid (PFOA) exposure was 0.75 (95% confidence interval [CI], 0.35-1.60; n = 2), and for perfluorooctane sulfonic acid (PFOS) was 1.76 (95% CI, 0.32-9.68; n = 1). The RR for gastric cancer and PFOA was 0.59 (95% CI, 0.28-1.21; n = 2) and PFAS was 0.96 (95% CI, 0.83-1.12; n = 2). The RR for colorectal cancer and PFOA was 0.83 (95% CI, 0.65-1.06; n = 6) and PFOS was 0.71 (95% CI, 0.22-2.27; n = 4). The RR for pancreatic cancer was 1.02 (95% CI, 0.90-1.15; n = 9) and PFOS was 0.92 (95% CI, 0.76-1.11; n = 2). Stratified analyses by geographical region, study design, quality score, year of publication, gender, and outcome revealed no associations for colorectal and pancreatic cancers. No dose-response trends were identified. Publication bias was suggested for gastric cancer. Conclusion Our study suggested no association between PFAS exposure and esophageal, gastric, colorectal, or pancreatic cancer. More rigorous research is needed to investigate this relationship in different settings, with precise PFAS quantification, a wider range of compounds, larger sample sizes for specific cancers, and better control for potential confounders. Our meta-analysis suggests inconclusive evidence, highlighting the need for further research.