Figure - available from: Cancers
This content is subject to copyright.
Chemical structures of Poly- and perfluoroalkylated substances. Structures are based on 2D structures from PubChem accessed 5 June 2022 and assembled in Chem-space.com accessed 5 June 2022.
Source publication
Simple Summary
Poly- and perfluoroalkylated substances (PFAS) are industrial chemicals found in many household products that persist in the environment. While several excellent review articles exist on the potential harmful effects of PFAS, there are few focused on cancer. This concise and streamlined mini-review focuses on summarizing molecular me...
Similar publications
The potential effects of poly- and perfluoroalkyl substances (PFAS) are a recently emergent human and environmental health concern. There is a consistent link between PFAS exposure and cancer, but the mechanisms are poorly understood. Although epidemiological evidence supporting PFAS exposure and cancer in general is conflicting, there is relativel...
Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals which could be associated with cancer development, such as kidney and testicular cancers, pancreatic and hepatocellular carcinoma and thyroid tumor. Available scientific literature offers no information on the role of PFAS in melanoma development/progression. Since 1965,...
Citations
... PFAS are fluorinated aliphatic chemicals that have been extensively studied also as carcinogens, since they can lead to hormonal disorders and cause epigenetic perturbations (75). Several studies have identified multiple sources of PFAS exposure for firefighters, such as aqueous film-forming foams, air and dust at the fire scene (76). ...
Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote several pathologies through different molecular mechanisms. Pollutants can affect the immune system and related pathways, perturbing its regulation and triggering pro-inflammatory responses. The exposure to several pollutants also leads to alterations in gut microbiota with a decreasing abundance of beneficial microbes, such as short-chain fatty acid-producing bacteria, and an overgrowth of pro-inflammatory species. The subsequent intestinal barrier dysfunction, together with oxidative stress and increased inflammatory responses, plays a role in the pathogenesis of gastrointestinal inflammatory diseases. Moreover, pollutants encourage the inflammation-dysplasia-carcinoma sequence through various mechanisms, such as oxidative stress, dysregulation of cellular signalling pathways, cell cycle impairment and genomic instability. In this narrative review, we will describe the interplay between pollutants, gut microbiota, and the immune system, focusing on their relationship with inflammatory bowel diseases and colorectal cancer. Understanding the biological mechanisms underlying the health-to-disease transition may allow the design of public health policies aimed at reducing the burden of disease related to pollutants.
... The exploration of options for PFAS control plans is paralleled by research efforts and advancements on the mechanisms of carcinogenicity. An emerging view is that there are distinct but interdependent general pathways of PFAS action involving, in particular, metabolism, endocrine disruption and epigenetic perturbation [115]. These three pathways seem mutually reinforcing and may combine to establish a pro-tumorigenic environment. ...
Background
Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018.
Methods
The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater.
Results
During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer.
Conclusions
For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.
... Both material's fabrication is scalable. Despite their numerous features, similar or distinct, the number of research publications seems to level off at around 3500 articles per year for mesoporous silica, but biochar is witnessing an However, the so-called "forever chemicals", namely perand poly-fluoroalkyl substances (PFAS), represent severe health issues such as endocrine disruption, pregnancy and lactation, immunosuppression and testicular cancer among other ones (Boyd et al. 2022). New approaches for mineralization exist, though some experiments have been proposed to be done in hot DMSO: water (Trang et al. 2022). ...
Summarizes latest developments and next-generation technologies for clean water production
Features sensors and removal of hazardous compounds as important aspects of clean water topic
Is a source of inspiration for next generations of clean water scientists and technologists
... The production of PFAS chemicals started in the mid-1900s and has been in continual use [1,2]. PFAS are widely present and persist in the environment, bioaccumulate in organisms, and are associated with several negative health outcomes, including increased serum cholesterol, adverse birth outcomes, and an increased risk of cancer [3][4][5][6][7][8][9]. Legacy PFAS perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are suspected carcinogens [7,8]. ...
... PFAS are widely present and persist in the environment, bioaccumulate in organisms, and are associated with several negative health outcomes, including increased serum cholesterol, adverse birth outcomes, and an increased risk of cancer [3][4][5][6][7][8][9]. Legacy PFAS perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are suspected carcinogens [7,8]. PFOA is a group 2B carcinogen, while PFOS and the newer, shorter chain PFAS hexafluoropropylene oxide (GenX) are EPA-classified as potentially carcinogenic [10][11][12]. ...
... Epidemiologic studies have indicated that the fetal gonads may be especially sensitive to pro-estrogenic and anti-androgenic insults [18][19][20][21]. Hence, TGCT etiology matches well with some of the most studied mechanisms of action of PFAS, namely, epigenetics and endocrine disruption (reviewed in [7,22]). Further, testicular cancer incidence rates have substantially increased since the introduction of industrial chemicals, including PFAS [23]. ...
The potential effects of poly- and perfluoroalkyl substances (PFAS) are a recently emergent human and environmental health concern. There is a consistent link between PFAS exposure and cancer, but the mechanisms are poorly understood. Although epidemiological evidence supporting PFAS exposure and cancer in general is conflicting, there is relatively strong evidence linking PFAS and testicular germ cell tumors (TGCTs). However, no mechanistic studies have been performed to date concerning PFAS and TGCTs. In this report, the effects of the legacy PFAS perfluorooctanesulfonic acid (PFOS) and the newer “clean energy” PFAS lithium bis(trifluoromethylsulfonyl)imide (LiTFSi, called HQ-115), on the tumorigenicity of TGCTs in mice, TGCT cell survival, and metabolite production, as well as gene regulation were investigated. In vitro, the proliferation and survival of both chemo-sensitive and -resistant TGCT cells were minimally affected by a wide range of PFOS and HQ-115 concentrations. However, both chemicals promoted the growth of TGCT cells in mouse xenografts at doses consistent with human exposure but induced minimal acute toxicity, as assessed by total body, kidney, and testis weight. PFOS, but not HQ-115, increased liver weight. Transcriptomic alterations of PFOS-exposed normal mouse testes were dominated by cancer-related pathways and gene expression alterations associated with the H3K27me3 polycomb pathway and DNA methylation, epigenetic pathways that were previously showed to be critical for the survival of TGCT cells after cisplatin-based chemotherapy. Similar patterns of PFOS-mediated gene expression occurred in PFOS-exposed cells in vitro. Metabolomic studies revealed that PFOS also altered metabolites associated with steroid biosynthesis and fatty acid metabolism in TGCT cells, consistent with the proposed ability of PFAS to mimic fatty acid-based ligands controlling lipid metabolism and the proposed role of PFAS as endocrine disrupters. Our data, is the first cell and animal based study on PFAS in TGCTs, support a pro-tumorigenic effect of PFAS on TGCT biology and suggests epigenetic, metabolic, and endocrine disruption as potential mechanisms of action that are consistent with the non-mutagenic nature of the PFAS class.
... PFAS have been associated with adverse health effects in humans including the elevated serum cholesterol and liver enzyme levels, immunosuppression and pregnancy complications (DeWitt et al. 2019;Blake and Fenton 2020;Steenland et al. 2020;Fenton et al. 2021). Epidemiological studies have further reported associations between serum PFAS-levels and a risk of tumors in many organs including kidney, bladder, testis, prostate, breast, ovarian, liver and immune tissue (non-Hodgkin lymphoma) (Vieira et al. 2013;Mastrantonio et al. 2018;Bartell and Vieira 2021;Boyd et al. 2022;Goodrich et al. 2022;Li et al. 2022a;Purdue et al. 2023). The risk has most often been described following exposures to long-chain PFAS (e.g., PFOA, PFOS, PFHxA, PFDA) whereas the risk after exposure to shortchain PFAS is less studied. ...
Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic persistent chemicals, which are used in many industrial and commercial applications. Hundreds of different PFAS have been identified in the environment and they are commonly found also in human blood. Due to the chemical stability and extensive use, PFAS pose a risk for human health and wildlife. Mounting evidence indicates that PFAS-exposure adversely affects many organs including liver, kidney, and reproductive tissues and induces tumors in laboratory rodents. Epidemiological studies show association between PFAS-exposure and some tumors also in humans. Effects of PFAS-exposure are complex and obviously do not depend only on the concentration and the structure of PFAS, but also on age and sex of the exposed individuals. It has been difficult to show a causal link between PFAS-exposure and tumors. Moreover, molecular mechanisms of the PFAS effects in different tissues are poorly understood. PFAS are not directly mutagenic and they do not induce formation of DNA binding metabolites, and thus are assumed to act more through non-genotoxic mechanisms. In this review, we discuss the involvement of PFAS-compounds in tumor development in tissues where PFAS exposure has been associated with cancer in epidemiological and animal studies (liver, kidney, testicle and breast). We will focus on molecular pathways and mechanisms related to tumor formation following PFAS-exposure.
... Conse quently, both wildlife and humans are subject to exposure to PFAS contamination (19)(20)(21)(22)(23)(24). Numerous epidemiological and mechanistic investigations have implied a connec tion between exposure to PFAS and a wide range of diseases, such as altered immune function, adverse reproductive effects, liver and kidney damage, obesity, and cancers (25)(26)(27)(28)(29)(30)(31). ...
Per- and polyfluoroalkyl substances (PFAS) are highly fluorinated synthetic organic compounds that have been used extensively in various industries owing to their unique properties. The PFAS family encompasses diverse classes, with only a fraction being commercially relevant. These substances are found in the environment, including in water sources, soil, and wildlife, leading to human exposure and fueling concerns about potential human health impacts. Although PFAS degradation is challenging, biodegradation offers a promising, eco-friendly solution. Biodegradation has been effective for a variety of organic contaminants but is yet to be successful for PFAS due to a paucity of identified microbial species capable of transforming these compounds. Recent studies have investigated PFAS biotransformation and fluoride release; however, the number of specific microorganisms and enzymes with demonstrable activity with PFAS remains limited. This review discusses enzymes that could be used in PFAS metabolism, including haloacid dehalogenases, reductive dehalogenases, cytochromes P450, alkane and butane monooxygenases, peroxidases, laccases, desulfonases, and the mechanisms of microbial resistance to intracellular fluoride. Finally, we emphasize the potential of enzyme and microbial engineering to advance PFAS degradation strategies and provide insights for future research in this field.
... While research suggests that PFAS are not directly mutagenic, numerous other carcinogenic mechanisms have been proposed. Three major proposed pathways of PFAS action are metabolism, endocrine disruption, and epigenetic perturbation [114]. They cause a wide range of biological changes in numerous carcinogenicity-related molecular pathways [115]. ...
Per- and polyfluoroalkyl substances (PFAS) belong to a group of synthetic compounds that have recently raised concerns about human health and environmental quality due to their great prevalence, degradation resistance, and potential toxicity. This review focuses on the applications of PFAS and their effects on human health. Specific emphasis has been laid on (i) the application/use of PFAS, (ii) sources and distribution of PFAS in diverse environmental compartments, and (iii) the impact of PFAS on human health. Significant health effects on humans are associated with exposure to PFAS, i.e., immunotoxicity, thyroid and kidney disorders, cancer, etc. Conclusions obtained from PFAS studies demonstrate that inadequate evidence should not be used to justify delaying risk reduction steps for PFAS alternatives. PFAS can be determined in different environmental matrices using both traditional analytical approaches, i.e., liquid chromatography coupled with mass spectrometry (LC-MS/MS) and semi-quantitative and passive sampling, and advanced analytical methods with colorimetric, spectrofluorimetric, and electrochemical detection. Traditional methods are costly and not broadly available, while the emerging, cost-effective methods are less sensitive and unable to meet regulatory exposure limits. There is still a significant number of studies to be performed to fully comprehend the real contamination by PFAS.
... Despite the growing recognition of non-mutagenic epigenetic pathways as pivotal in the biological effects of PFAS, research in this domain has been relatively limited, primarily focusing on DNA methylation [241][242][243]. PFAS exposure has been associated with both hypomethylation and hypermethylation in genome-wide and gene-specific molecular epidemiology studies. ...
Simple Summary
This exploratory narrative review investigates the association between exposure to per- and polyfluoroalkyl substances (PFAS), sociodemographic factors, stressors, and endometrial cancer risk. It explores the diverse sources of PFAS exposure and examines the role of income, education, occupation, ethnicity, and geographic location in influencing exposure levels and cancer risk. The review finds significant correlations between these sociodemographic factors and both PFAS exposure and endometrial cancer risk. It emphasizes the need for further interdisciplinary research and targeted interventions to understand and address these complex relationships, highlighting the importance of addressing health disparities for effective disease prevention and management.
Abstract
This exploratory narrative review paper delves into the intricate interplay between per- and polyfluoroalkyl substances (PFAS) exposure, sociodemographic factors, and the influence of stressors in the context of endometrial cancer. PFAS, ubiquitous environmental contaminants notorious for their persistence in the ecosystem, have garnered attention for their potential to disrupt endocrine systems and provoke immune responses. We comprehensively examine the various sources of PFAS exposure, encompassing household items, water, air, and soil, thus shedding light on the multifaceted routes through which individuals encounter these compounds. Furthermore, we explore the influence of sociodemographic factors, such as income, education, occupation, ethnicity/race, and geographical location and their relationship to endometrial cancer risk. We also investigated the role of stress on PFAS exposure and endometrial cancer risk. The results revealed a significant impact of sociodemographic factors on both PFAS levels and endometrial cancer risk. Stress emerged as a notable contributing factor influencing PFAS exposure and the development of endometrial cancer, further emphasizing the importance of stress management practices for overall well-being. By synthesizing evidence from diverse fields, this review underscores the need for interdisciplinary research and targeted interventions to comprehensively address the complex relationship between PFAS, sociodemographic factors, stressors, and endometrial cancer.
... To date, several epidemiological studies have reported that PFAS exposure is associated with human health outcomes, such as metabolic syndrome [10], cardiovascular events [11], and cancer [12]. A growing number of studies have revealed that PFASs can disrupt sex hormones and affect bone cell differentiation, ultimately resulting in enhanced bone resorption [13][14][15][16], which is similar to the important features of periodontitis. ...
Objectives
To investigate the association between serum per- and polyfluoroalkyl substances (PFAS) and periodontitis, and further explore the possible mediating role of sex hormones in this association.
Methods
We extracted data from National Health and Nutrition Examination Survey (NHANES) 2009–2014. Univariable and multivariable logistic regression models were performed to investigate the association between serum levels of seven PFASs and periodontitis. Bayesian kernel machine regression (BKMR) was conducted to assess the joint effect of PFASs in mixtures. Mediation analyses were used to explore the potential mediating role of sex hormones.
Results
Participants with periodontitis had higher concentrations of serum perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) than those without periodontitis (both P < 0.05). In fully adjusted models, high serum concentrations of PFOS and PFNA were positively associated with periodontitis (tertile 3 vs. tertile 1: prevalence ratio (PR) = 1.19 for PFOS, 95% CI: 1.01–1.39; PR = 1.17 for PFNA, 95% CI: 1.02–1.34). The results from the BKMR models consistently showed a positive association between PFAS mixtures and periodontitis. Of note, testosterone and the ratio of testosterone to estradiol significantly mediated the relationship between high level of PFOS and periodontitis, accounting for 16.5% and 31.7% of the total effect, respectively. Sensitivity analyses yielded similar results when using periodontal clinical indices (mean loss of attachment, mean periodontal probing depth, and the number of teeth) as dependent variables.
Conclusions
These findings provide evidence to support a positive association between certain PFASs and periodontitis, which might be partially mediated by sex hormones.
... 20,21 Certain cancers such as liver, prostrate or testicular cancer have been linked to PFAS mediated PPAR-α disruption and epigenetic changes. 22,23 PFAS is also detected in brain tissue and cerebrospinal fluid. 24,25 Perfluorocarboxylates and perfluorosulfates with 6-14 carbon chains were detected in rodents, fish, and bears, with the longer chain PFAS generally occurring at higher concentrations. ...
Per- and polyfluorinated alkyl substances (PFAS) are ubiquitous in most environments, accumulate in several tissues, and can adversely affect human health. PFAS have been implicated in neurodegenerative and behavioral disorders. However, the mechanisms through which PFAS accumulation in neurons affects biological function remain unknown. In this study, SH-SY5Y neuroblastoma cells were used to investigate how perfluorooctanoic acid (PFOA), perfluorooctansulfonic acid (PFOS), perfluorodecanoic acid (PFDA) perfluorodecanesulfonic acid (PFDS), 8:2 fluorotelomer sulfate (8:2 FTS) and 8:2 fluorotelomer alcohol (8:2 FTOH) exposures influence neuronal health. After a 30 μM-, 24-hour exposure, cells accumulated up to 800 ng PFAS/mg protein. Transcriptomics analysis of control and PFAS-exposed cells revealed 721 genes were differentially expressed across six treatments (p adj < 0.05). Eleven of these differentially expressed genes were observed for all treatments, suggesting that these genes are potential markers for neuronal PFAS exposure. In PFOA-treated cells, we observed multiple downregulated genes are enriched for functions related to synaptic growth and neural function. In contrast, upregulated genes in PFOS, PFDS, FTS, and FTOH-treated cells showed enrichment in functions related to response to hypoxia and amino acid metabolism. Overall, our results highlight specific biological processes that potentially underlie negative effects of PFAS on neuronal health.
Synopsis
Per- and poly fluorinated alkyl substances (PFAS) have been shown to bioaccumulate in human tissues and affect health. This study aims to provide insight into the specific biological processes by which PFAS exposure affects neuronal cells.
