Per- and Poly-fluoroalkyl Substances (PFAS) Exposure and Risk of Kidney, Liver, and Testicular Cancers: A Systematic Review and Meta-Analysis
Contenuto principale dell'articolo
Keywords
Abstract
Introduction: Per- and poly-fluoroalkyl substances (PFASs) are a large, complex group of synthetic chemicals humans can be exposed to from occupational or environmental sources. In this systematic review and meta-analysis, we examined the association between PFAS exposure, particularly Perfluorooctanoic Acid (PFOA), and Perfluorooctane Sulfonic Acid (PFOS), and risk of kidney, liver, and testicular cancer. Methods: We systematically searched PubMed to identify cohort and case-control studies reported after the Monograph of the International Agency for Research on Cancer and the Toxicological Profile of the Agency for Toxic Substances and Disease Registry. We assessed the quality of the studies by using a modified version of the Newcastle-Ottawa Scale (NOS). Forest relative risk (RR) plots were constructed for liver, kidney, and testicular cancer. We conducted stratified analyses by geographic region, study design, quality score, outcome, years of publication, exposure source, and PFAS type. A random-effects model was used to address heterogeneity between studies. Results: Fifteen studies, including ten cohort studies, three case-control studies nested in a cohort, and two case-control studies were included after removing duplicate and irrelevant reports. We found an association between overall PFAS exposure and the risk of kidney cancers (RR=1.18, 95% CI =1.05-1.32; I =52.8%, 11 studies). Also, we showed an association between high-level exposure to PFAS and kidney cancer (RR=1.74, 95% CI =1.23-2.47; p=0.005) and testicular cancer (RR=2.22, 95% CI =1.12-4.39; p=0.057). There was no association with liver cancer. We found no heterogeneity by geographical region, PFAS type, study design, outcome, quality score, year of publication, or exposure source. Only two studies reported results among women. Conclusions: We detected an association between overall PFAS exposure and kidney cancer and high doses of PFAS with testicular cancer. However, bias and confounding cannot be excluded, precluding a conclusion in terms of causality.
Riferimenti bibliografici
2. Gaines LGT. Historical and current usage of per- and polyfluoroalkyl substances (PFAS): A liter-ature review. Am J Ind Med. 2023;66:353-378.
3. Exner M, Färber H. Perfluorinated surfactants in surface and drinking waters. Environ Sci Pollut Res 2006:13;299-307.
4. Panieri E, Baralic K, Djukic-Cosic D, Buha Djordjevic A, Saso L. PFAS Molecules: A Major Concern for the Human Health and the Environment. Toxics. 2022;10:44.
5. European Environment Agency. 2019.Emerging chemical risks in Europe - PFAS. Copenhagen, EEA, 2019. [https://www.eea.europa.eu/themes/human/chemicals/emerging-chemical-risks-in-europe]
6. Fenton SE, Ducatman A, Boobis A, et al. Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research. Envi-ron Toxicol Chem. 2021;40:606-630.
7. Steenland K, Winquist A. PFAS and cancer, a scoping review of the epidemiologic evidence. Envi-ron Res. 2021;194:110690.
8. International Agency for Research on Cancer. PFOA. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, vol. 110. Some Chemicals Used as Solvents and in Polymer Manu-facture. Lyon, IARC, 2017, pp. 37-110.
9. Ding N, Harlow SD, Randolph JF Jr, Loch-Caruso R, Park SK. Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary. Hum Reprod Update. 2020;26:724-752.
10. Chang ET, Adami HO, Boffetta P, Wedner HJ, Mandel JS. A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and immunological health conditions in humans. Crit Rev Toxicol 2016;46:279-331.
11. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-249.
12. Agency for Toxic Substances and Disease Registry. Toxicological Profile for Perfluoroalkyls. Atlanta, GA, ATSDR, 2021.
13. von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)statement: guidelines for reporting observational studies. J Clin Epi-demiol. 2008;61:344-9.
14. Moher D, Liberati A; Tetzlaff J, Altmann DG. The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. Ann Intern Med 2009;151:264-69.
15. Stan, A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010;25:603-605.
16. Higgins JP; Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat. Med. 2002;21:1539-1558.
17. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-88.
18. Egger M, Davey Smith G, Schneider M, Minder CE. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629-34.
19. Gilliland FD, Mandel JS. Mortality among employees of a perfluorooctanoic acid production plant. J Occup Med. 1993;35:950-4.
20. Alexander BH, Olsen GW, Burris JM, Mandel JH, Mandel JS. Mortality of employees of a perfluo-rooctanesulphonyl fluoride manufacturing facility. Occup Environ Med. 2003;60:722-9.
21. Leonard RC, Kreckmann KH, Sakr CJ, Symons JM. Retrospective cohort mortality study of work-ers in a polymer production plant including a reference population of regional workers. Ann Epi-demiol. 2008;18:15-22.
22. Eriksen KT, Sørensen M, McLaughlin JK, et al. Perfluorooctanoate and perfluorooctanesulfonate plasma levels and risk of cancer in the general Danish population. J Natl Cancer Inst. 2009;101:605-9.
23. Steenland K, Woskie S. Cohort mortality study of workers exposed to perfluorooctanoic acid. Am J Epidemiol. 2012;176:909-17.
24. Vieira VM, Hoffman K, Shin HM, Weinberg JM, Webster TF, Fletcher T. Perfluorooctanoic acid ex-posure and cancer outcomes in a contaminated community: a geographic analysis. Environ Health Perspect. 2013;121:318-23.
25. Barry V, Winquist A, Steenland K. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect. 2013;121:1313-8.
26. Raleigh KK, Alexander BH, Olsen GW, et al. Mortality and cancer incidence in ammonium perfluo-rooctanoate production workers. Occup Environ Med. 2014;71:500-6.
27. Mastrantonio M, Bai E, Uccelli R, Cordiano V, Screpanti A, Crosignani P. Drinking water contami-nation from perfluoroalkyl substances (PFAS): an ecological mortality study in the Veneto Re-gion, Italy. Eur J Public Health. 2018;28:180-185.
28. Girardi P, Merler E. A mortality study on male subjects exposed to polyfluoroalkyl acids with high internal dose of perfluorooctanoic acid. Environ Res. 2019;179:108743.
29. Shearer JJ, Callahan CL, Calafat AM, et al. Serum Concentrations of Per- and Polyfluoroalkyl Sub-stances and Risk of Renal Cell Carcinoma. J Natl Cancer Inst. 2021;113:580-587.
30. Li H, Hammarstrand S, Midberg B, et al. Cancer incidence in a Swedish cohort with high exposure to perfluoroalkyl substances in drinking water. Environ Res. 2022;204:112217.
31. Cao L, Guo Y, Chen Y, Hong J, Wu J, Hangbiao J. Per-/polyfluoroalkyl substance concentrations in human serum and their associations with liver cancer. Chemosphere. 2022;296:134083.
32. Goodrich JA, Walker D, Lin X, et al. Exposure to perfluoroalkyl substances and risk of hepatocel-lular carcinoma in a multiethnic cohort. JHEP Rep. 2022;4:100550.
33. Law HD, Armstrong BK, D’este C, et al. Relative rates of cancers and deaths in Australian commu-nities with PFAS environmental contamination associated withfire-fighting foams: A cohort study using linked data. Cancer Epidemiol. 2023;82:102296.
34. Li Y, Xu Y, Scott K, et al. Half-lives of PFOA, PFPeS, PFHxS, PFHpS and PFOS after end of exposure to contaminated drinking water. Environ Epidemiol 2019;3:237.
35. Li Y, Fletcher T, Mucs D, et al. Half-lives of PFOS, PFHxS and PFOA after end of exposure to con-taminated drinking water. Occup Environ Med. 2018;75:46-51.
36. Brennan NM, Evans AT, Fritz MK, Peak SA, von Holst HE. Trends in the Regulation of Per- and Polyfluoroalkyl Substances (PFAS): A Scoping Review. Int J Environ Res Public Health. 2021;18:10900.
37. Fenton SE, Ducatman A, Boobis A, et al. Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research. Envi-ron Toxicol Chem. 2021;40:606-630.
38. Wen LL, Lin CY, Chou HC, Chang CC, Lo HY, Juan SH. Perfluorooctanesulfonate mediates renal tub-ular cell apoptosis through PPARgamma inactivation. PLoS One 2016;11:e0155190.
39. Stanifer JW, Stapleton HM, Souma T, Wittmer A, Zhao X, Boulware LE. Perfluorinated chemicals as emerging environmental threats to kidney health: A scoping review. Clin J Am Soc Nephrol 2018;13:1479-1492.
40. Wan HT, Zhao YG, Wei X, Hui KY, Giesy JP, Wong CK. PFOS-induced hepatic steatosis, the mecha-nistic actions on beta-oxidation and lipid transport. Biochim Biophys Acta 2012;1820:1092-1101.
41. Hui Z, Li R, Chen L. The impact of exposure to environmental contaminant on hepatocellular lipid metabolism. Gene. 2017;622:67-71.
42. Massoud O, Charlton M. Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and hepatocellular carcinoma. Clin Liver Dis. 2018;22:201–211.
43. Grandjean P, Heilmann C, Weihe P, Nielsen F, Mogensen UB, Budtz-Jorgensen E. Serum vaccine an-tibody concentrations in adolescents exposed to perfluorinated compounds. Environ Health Perspect 2017;125:077018.
44. Coperchini F, Awwad O, Rotondi M, Santini F, Imbriani M, Chiovato L. Thyroid disruption by per-fluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). J Endocrinol Invest. 2017;40:105-121.
45. Barry V, Winquist A, Steenland K. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect. 2013;121:1313-1318.
46. Sabovic I, Cosci I, De Toni L, et al. Perfluoro-octanoic acid impairs sperm motility through the al-teration of plasma membrane. J Endocrinol Invest 2020;43:641-652.
47. Cheng L, Albers P, Berney DM, et al. Testicular cancer. Nat Rev Dis Primers. 2018;4:29.
48. Di Nisio A, Rocca MS, Sabovic I, et al. Perfluorooctanoic acid alters progesterone activity in human endometrial cells and induces reproductive alterations in young women. Chemosphere. 2020;242:125208.
49. Scelo G, Larose TL. Epidemiology and Risk Factors for Kidney Cancer. J Clin Oncol. 2018;36:3574-3581.
50. McGlynn KA, Trabert B. Adolescent and adult risk factors for testicular cancer. Nat Rev Urol. 2012;9:339-49.
51. Imir OB, Kaminsky AZ, Zuo QY, et al. Per- and Polyfluoroalkyl Substance Exposure Combined with High-Fat Diet Supports Prostate Cancer Progression. Nutrients. 2021;13:3902
Barra laterale dell'articolo
Dettagli dell'articolo
Come citare
Questo volume è pubblicato con la licenza Creative Commons Attribuzione 4.0 Internazionale.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reproductions with commercial intent will require written permission and payment of royalties.
This work is licensed under a CC BY-NC-SA 4.0 Creative Commons Attribution-NonCommercial ShareAlike 4.0 International License.
Monireh Sadat Seyyedsalehi, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
Paolo Boffetta, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA
Department of Family, Population and Preventive Medicine, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, USA
Come citare
