Zhang Sirui, Kappil Elizabeth Maria, Zheng Tongzhang, Boffetta Paolo, Seyyedsalehi Monireh Sadat
Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA.
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Eur J Cancer Prev. 2025 Sep 1;34(5):445-455. doi: 10.1097/CEJ.0000000000000935. Epub 2024 Dec 9.
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.
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.
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.
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.
全氟和多氟烷基物质（PFASs）是自20世纪40年代以来用于工业和消费应用的一类合成化学品。已知或怀疑这些物质会致癌，尤其是肾癌和睾丸癌。然而，它们与其他类型癌症的关联尚不清楚。本综述旨在研究PFAS暴露与其他癌症风险之间的联系，包括胃肠道癌症，如食管癌、胃癌、结直肠癌和胰腺癌。
我们对来自国际癌症研究机构专论、有毒物质和疾病登记机构文件以及PubMed（截至2024年1月）的文献进行了系统综述，重点关注PFAS暴露与胃肠道癌症之间的关联。四名独立评审员筛选了研究，提取了信息，并使用改良的纽卡斯尔-渥太华量表评估了研究质量。采用随机效应模型进行荟萃分析，包括分层分析和剂量反应评估。
荟萃分析纳入了17项研究。全氟辛酸（PFOA）暴露导致食管癌的汇总相对风险（RR）为0.75（95%置信区间[CI]，0.35 - 1.60；n = 2），全氟辛烷磺酸（PFOS）为1.76（95% CI，0.32 - 9.68；n = 1）。PFOA导致胃癌的RR为0.59（95% CI，0.28 - 1.21；n = 2），PFAS为0.96（95% CI，0.83 - 1.12；n = 2）。PFOA导致结直肠癌的RR为0.83（95% CI，0.65 - 1.06；n = 6），PFOS为0.71（95% CI，0.22 - 2.27；n = 4）。胰腺癌的RR为1.02（95% CI，0.90 - 1.15；n = 9），PFOS为0.92（95% CI，0.76 - 1.11；n = 2）。按地理区域、研究设计、质量评分、出版年份、性别和结局进行的分层分析显示，结直肠癌和胰腺癌无关联。未发现剂量反应趋势。提示胃癌存在发表偏倚。
我们的研究表明PFAS暴露与食管癌、胃癌、结直肠癌或胰腺癌之间无关联。需要更严格的研究来在不同环境中调查这种关系，精确量化PFAS，研究更广泛的化合物，针对特定癌症增加样本量，并更好地控制潜在混杂因素。我们的荟萃分析结果证据不确凿，突出了进一步研究的必要性。
