Detection of Persistent Organic Pollutants in Omental Adipose Tissue from Patients with Diffuse-Gastric Cancer: A Pilot Study

Perrot‐Applanat, Martine; Pimpie, Cynthia; Cano-Sancho, Germán; Antignac, Jean‐Philippe; Pocard, Marc

doi:10.3390/cancers13194874

Cited by 5 publications

(5 citation statements)

References 55 publications

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“…Whether or not the increase of CYP1s expression that we observed in diffuse as compared to intestinal GC is due to exposure to a specific or to multiple POPs remains to be established [64]. We have previously reported the significant and widespread increase of a substantial set of POPs such as polychlorinated dioxins (PCDDs/PCDFs), polychlorobiphenyls (PCBs) and polybrominated flame retardants (such as PBDE 209, a carcinogenic intermediate of BaP) in human omental tissue (fat deposits) from French patients with diffuse-GC, as compared to control biopsies [13]. Coexposure of TCDD and PBDE209 was observed in 33% of the omentum from patients with diffuse GC.…”

Section: Discussionmentioning

confidence: 99%

“…It is also known that polycyclic polyhalogenated hydrocarbons (like dioxins and PCBs) and polycyclic aromatic hydrocarbons (PAHs) including benzo[a]pyrene from tobacco-smoke and biomass burning) may link to relatively high health risk including cancers. We have previously shown that environmental chemicals such as persistent organic pollutants (POPs) are involved in breast cancers [12], and may accumulate in the Omentum adipose tissue of patients with GC [13]. In addition to TCDD, the prototypical and most potent known environmental ligand in animals and humans, other widespread environmental POPs contaminants bind aryl hydrocarbon receptor (AhR, a basic helix-loop-helix transcription factor) with strong affinities [14,15] and may chronically activate AhR in cancer agression.…”

Section: Introductionmentioning

confidence: 99%

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High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

Perrot-Applanat,

Pimpie,

Vacher

et al. 2024

Preprint

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Diffuse type of gastric cancer (GC) has an increasing prevalence worldwide, especially in Western countries, is usually diagnosed at advanced stages, and has no efficacious treatment options. Epidemiological studies have reported an increased mortality from GC after occupational exposure to well-studied pro-carcinogen that are metabolically activated by Cyp P450 enzymes through aryl hydrocarbon receptor (AhR). Substantial studies support the involvement of AhR in gastric carcinogenesis. However, little is known about the role of AhR in diffuse GC, as compared to intestinal GC. In a cohort of 29 gastric tumors, we described a significantly increased AhR protein and mRNA expression levels in GCs, independently of subtypes and clinical parameters. AhR and RhoA mRNA expression were correlated in diffuse GC. Further, our study characterized how AhR affects gene expression in diffuse GC. Using qRT-PCR, we compared the expression levels of AhR, Cyp1A1 and Cyp1B1 to the expression of genes in a panel previously described. In diffuse GC, Cyp1A1 expression correlated with genes involved in IGF signalling, EMT (VIM), migration (MMP2). In an in vitro assay using the poorly differentiated KATOIII epithelial cell line, two well-known ligands for AhR (TCDD and BaP) induced mRNA expression of CYP1A1, IL1b, as well as UGT1, NQO1 and AhRR to a lower extent. We also observed a strong increase in Cyp1B1 expression in diffuse GC, along with a lower TCDD-increased Cyp1B1 expression as compared to Cyp1A1 in KATOIII cells, and immunostaining in stromal cells. In intestinal GC, Cyp1B1 inversely correlated with several genes including IDO1 (generating endogenous kynurenin-e AhR ligand). Our data provide evidence for a major role of AhR in GC, as an environmental xenobiotics receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support continued efforts to clarify the identities of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

Perrot-Applanat,

Pimpie,

Vacher

et al. 2024

Preprint

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“…Perrot‐Applanat et al. ( 2021 ) analysed BDE‐28 , ‐ 47 , ‐ 99 , ‐ 100 , ‐ 153 , ‐ 154 , ‐ 183 , ‐ 209 and a number of further POPs in greater omentum samples from 32 patients (16 men and 16 women). The pilot study included 14 patients with diffuse‐gastric cancer, 10 patients with other cancers (ovary or colon) that had metastasised in the peritoneal cavity and 8 patients operated for non‐cancer diseases serving as a control.…”

Section: Assessmentmentioning

confidence: 99%

“…The authors stated that the interpretation of the study was limited by a relatively large interindividual variation in the levels of the measured congeners, probably due to the heterogeneity in the study populations age and pretrial dietary habits. Perrot-Applanat et al (2021) analysed BDE-28, -47, -99, -100, -153, -154, -183, -209 and a number of further POPs in greater omentum samples from 32 patients (16 men and 16 women). The pilot study included 14 patients with diffusegastric cancer, 10 patients with other cancers (ovary or colon) that had metastasised in the peritoneal cavity and 8 patients operated for non-cancer diseases serving as a control.…”

Section: Other Human Tissuesmentioning

confidence: 99%

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

Schrenk,

Bignami,

Bodin

et al. 2024

EFS2

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The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE‐28, ‐47, ‐49, ‐99, ‐100, ‐138, ‐153, ‐154, ‐183 and ‑209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE‐47, ‐99, ‐153, ‐209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint‐specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

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“…Human studies support the association of various OCPs (aldrin, dieldrin, endosulfan, HCH, DDT, 2,4,5-trichlorophenoxyacetic acid, phenoxy acid herbicides, and methoxychlor). The exposure (both occupational and non-occupational) has been strongly linked to increased incidence of non-Hodgkin’s lymphoma [ 22 ]; multiple myeloma [ 23 ]; soft tissue sarcomas [ 24 ]; lung cancers [ 25 ]; and cancers of the pancreas, stomach, liver, and kidney as well as urinary and gall bladder cancer [ 26 , 27 , 28 , 29 , 30 ].…”

Section: Carcinogenic Effects Of Organochlorine Pesticidesmentioning

confidence: 99%

Xeno-Estrogenic Pesticides and the Risk of Related Human Cancers

Kumar

Yadav

Banerjee

2022

JoX

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In recent decades, “environmental xenobiotic-mediated endocrine disruption”, especially by xeno-estrogens, has gained a lot of interest from toxicologists and environmental researchers. These estrogen-mimicking chemicals are known to cause various human disorders. Pesticides are the most heavily used harmful xenobiotic chemicals around the world. The estrogen-mimicking potential of the most widely used organochlorine pesticides is well established. However, their effect is not as clearly understood among the plethora of effects these persistent xenobiotics are known to pose on our physiological system. Estrogens are one of the principal risk modifiers of various disorders, including cancer, not only in women but in men as well. Despite the ban on these xenobiotics in some parts of the world, humans are still at apparent risk of exposure to these harmful chemicals as they are still widely persistent and likely to stay in our environment for a long time owing to their high chemical stability. The present work intends to understand how these harmful chemicals may affect the risk of the development of estrogen-mediated human cancer.

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Detection of Persistent Organic Pollutants in Omental Adipose Tissue from Patients with Diffuse-Gastric Cancer: A Pilot Study

Cited by 5 publications

References 55 publications

High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

High Expression of AhR and Environmental Pollution As AhR Linked Ligands Impact on Oncogenic Signaling Pathways in Western Patients With Diffuse Gastric Cancers. A Pilot Study

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food

Xeno-Estrogenic Pesticides and the Risk of Related Human Cancers

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