{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:07:12Z","timestamp":1783418832121,"version":"3.54.6"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian National Laboratory Project","award":["RRF-2.3.1-21-2022-00007"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Endometrial cancer is one of the most common cancer types among women. Many factors can contribute to the development of this disease, including environmental factors and, thus, eating habits. Our study aims to determine the levels of various mycotoxins and their metabolites in the blood serum and endometrial tissue samples of participants with previously proven endometrial cancer and to find possible contributions to cancer development. In the cohort clinical trial, 52 participants aged between 44 and 86 were studied. The participants were divided into two groups: patients or matched controls. All patients had previously histologically diagnosed endometrial cancer. The cancer patients were divided into low-grade endometrioid and low- plus high-grade endometrioid groups. Controls had no history of endometrial malignancy or premalignancy. Blood serum and endometrial tissue samples were obtained from all study patients. We compared the concentrations of total Aflatoxins (Afs), Deoxynivalenol (DON), Ochratoxin-A (OTA), T2-toxin and HT2 toxin (T2\/HT2 toxin), Zearalenone (ZEN), alpha-Zearalenol (\u03b1-ZOL), and Fumonisin B1 (FB1) in the serum and endometrium between the different study groups. As a result, we can see a significant correlation between the higher levels of Afs and zearalenone and the presence of endometrial cancer. In the case of Afs, DON, OTA, T2\/HT2 toxins, ZEN, and alpha-ZOL, we measured higher endometrial concentrations than in serum. Considering the effect of mycotoxins and eating habits on cancer development, our results might lead to further research exploring the relationship between certain mycotoxins and endometrium cancer.<\/jats:p>","DOI":"10.3390\/toxins16060236","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T09:04:25Z","timestamp":1716455065000},"page":"236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Possible Role of Mycotoxins in the Pathogenesis of Endometrial Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"M\u00e1rk\u00f3","family":"Unicsovics","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, 1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0437-6433","authenticated-orcid":false,"given":"Zs\u00f3fia","family":"Moln\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Animal Biotechnology, Agribiotechnology and Precision Breeding for Food Security National Laboratory, Institute of Genetics and Biotechnology, Hungarian University of Agriculture and Life Sciences, 2100 G\u00f6d\u00f6ll\u0151, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2323-833X","authenticated-orcid":false,"given":"Mikl\u00f3s","family":"M\u00e9zes","sequence":"additional","affiliation":[{"name":"Department of Feed Safety, Institute of Physiology and Nutrition, Hungarian University of Agriculture and Life Sciences, 2100 G\u00f6d\u00f6ll\u0151, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2790-1741","authenticated-orcid":false,"given":"Katalin","family":"Posta","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Applied Biotechnology, Institute of Genetics and Biotechnology, Hungarian University of Agriculture and Life Sciences, 2100 G\u00f6d\u00f6ll\u0151, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Nagy\u00e9ri","sequence":"additional","affiliation":[{"name":"Department of Animal Biotechnology, Agribiotechnology and Precision Breeding for Food Security National Laboratory, Institute of Genetics and Biotechnology, Hungarian University of Agriculture and Life Sciences, 2100 G\u00f6d\u00f6ll\u0151, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs","family":"V\u00e1rb\u00edr\u00f3","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, 1088 Budapest, Hungary"},{"name":"Department of Obstetrics and Gynecology, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1919-1869","authenticated-orcid":false,"given":"N\u00e1ndor","family":"\u00c1cs","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, 1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9876-126X","authenticated-orcid":false,"given":"Levente","family":"S\u00e1ra","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Semmelweis University, 1088 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9302-1115","authenticated-orcid":false,"given":"Zsuzsanna","family":"Sz\u0151ke","sequence":"additional","affiliation":[{"name":"Department of Animal Biotechnology, Agribiotechnology and Precision Breeding for Food Security National Laboratory, Institute of Genetics and Biotechnology, Hungarian University of Agriculture and Life Sciences, 2100 G\u00f6d\u00f6ll\u0151, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gruber-Dorninger, C., Jenkins, T., and Schatzmayr, G. (2019). Global Mycotoxin Occurrence in Feed: A Ten-Year Survey. Toxins, 11.","DOI":"10.3390\/toxins11070375"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111161","DOI":"10.1016\/j.fct.2020.111161","article-title":"Toxicity of mycotoxins in vivo on vertebrate organisms: A review","volume":"137","author":"Cimbalo","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.toxicon.2020.04.101","article-title":"Mycotoxins, invisible danger of feedstuff with toxic effect on animals","volume":"182","year":"2020","journal-title":"Toxicon"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ekwomadu, T., Mwanza, M., and Musekiwa, A. (2022). Mycotoxin-Linked Mutations and Cancer Risk: A Global Health Issue. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19137754"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kobets, T., Smith, B.P.C., and Williams, G.M. (2022). Food-Borne Chemical Carcinogens and the Evidence for Human Cancer Risk. Foods, 11.","DOI":"10.3390\/foods11182828"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s12550-016-0265-7","article-title":"Mycotoxins as human carcinogens-the IARC Monographs classification","volume":"33","author":"Ostry","year":"2017","journal-title":"Mycotoxin Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/ijgo.14969","article-title":"Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies","volume":"164","author":"Yang","year":"2024","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alexa, M., Hasenburg, A., and Battista, M.J. (2021). The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions. Cancers, 13.","DOI":"10.3390\/cancers13061478"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7706","DOI":"10.21037\/tcr-20-2334","article-title":"Endometrial cancer: A genetic point of view","volume":"9","author":"Bianco","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.mrgentox.2013.06.019","article-title":"Somatic changes in primary liver cancer in Russia: A pilot study","volume":"755","author":"Kalinina","year":"2013","journal-title":"Mutat. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.taap.2017.12.011","article-title":"Ochratoxin A exposure decreased sperm motility via the AMPK and PTEN signaling pathways","volume":"340","author":"Zhang","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"993","DOI":"10.5713\/ajas.20.0292","article-title":"Zearalenone exposure affects the Wnt\/\u03b2-catenin signaling pathway and related genes of porcine endometrial epithelial cells in vitro","volume":"34","author":"Song","year":"2021","journal-title":"Anim. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41379-022-01102-x","article-title":"p53 immunohistochemistry in endometrial cancer: Clinical and molecular correlates in the PORTEC-3 trial","volume":"35","author":"Vermij","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.canlet.2009.02.057","article-title":"The aflatoxin-induced TP53 mutation at codon 249 (R249S): Biomarker of exposure, early detection and target for therapy","volume":"286","author":"Gouas","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_15","first-page":"399","article-title":"Aflatoxin B1 Alters the Expression of p53 in Cytochrome P450-Expressing Human Lung Cells","volume":"89","author":"Watterson","year":"2005","journal-title":"Toxicol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1007\/s00216-017-0807-7","article-title":"The determination of zearalenone and its major metabolites in endometrial cancer tissues","volume":"410","author":"Pajewska","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_17","first-page":"177","article-title":"Density of blood","volume":"4","author":"Shmukler","year":"2004","journal-title":"Phys. Factb."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Guerre, P. (2020). Mycotoxin and Gut Microbiota Interactions. Toxins, 12.","DOI":"10.3390\/toxins12120769"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"181","DOI":"10.6004\/jnccn.2023.0006","article-title":"Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology","volume":"21","author":"Yashar","year":"2023","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1472-8206.1988.tb00635.x","article-title":"Drug pharmacokinetics in the obese","volume":"2","author":"Cheymol","year":"1988","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lootens, O., De Boevre, M., Ning, J., Gasthuys, E., Van Bocxlaer, J., De Saeger, S., and Vermeulen, A. (2023). Building a Human Physiologically Based Pharmacokinetic Model for Aflatoxin B1 to Simulate Interactions with Drugs. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030894"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1080\/02652030701546180","article-title":"Absorption, distribution, and elimination of fumonisin B1 metabolites in weaned piglets","volume":"25","author":"Fodor","year":"2008","journal-title":"Food Addit. Contam."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1507\/endocrj.KR-114","article-title":"Biological roles of estrogen and progesterone in human endometrial carcinoma\u2013new developments in potential endocrine therapy for endometrial cancer","volume":"54","author":"Ito","year":"2007","journal-title":"Endocr. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00432-003-0427-9","article-title":"Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer","volume":"129","author":"Berstein","year":"2003","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2019.04.008","article-title":"Biology and clinical relevance of Hydroxysteroid (17beta) dehydrogenase enzymes","volume":"489","author":"Poutanen","year":"2019","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"61225","DOI":"10.1007\/s11356-021-12641-2","article-title":"Content of total aflatoxin, lead, and cadmium in the bovine meat and edible offal: Study of their human dietary intake, health risk assessment, and molecular biomarkers","volume":"28","author":"Aljazzar","year":"2021","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gramantieri, L., Gnudi, F., Vasuri, F., Mandrioli, D., Fornari, F., Tovoli, F., Suzzi, F., Vornoli, A., D\u2019Errico, A., and Piscaglia, F. (2022). Aflatoxin B1 DNA-Adducts in Hepatocellular Carcinoma from a Low Exposure Area. Nutrients, 14.","DOI":"10.3390\/nu14081652"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.tox.2008.03.005","article-title":"Tissue distribution and proinflammatory cytokine induction by the trichothecene deoxynivalenol in the mouse: Comparison of nasal vs. oral exposure","volume":"248","author":"Amuzie","year":"2008","journal-title":"Toxicology"},{"key":"ref_29","first-page":"313","article-title":"Blood, breast milk and urine: Potential biomarkers of exposure and estimated daily intake of ochratoxin A: A review","volume":"33","author":"Soto","year":"2016","journal-title":"Food Addit. Contam. Part A"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/17450390500147594","article-title":"Influence of organically or conventionally produced wheat on health, performance and mycotoxin residues in tissues and bile of growing pigs","volume":"59","author":"Schneweis","year":"2005","journal-title":"Arch. Anim. Nutr."},{"key":"ref_31","first-page":"393","article-title":"Toxicological approaches to the metabolities of fusaria. XII. Fate and distribution of T-2 toxin in mice","volume":"48","author":"Matsumoto","year":"1978","journal-title":"Jpn. J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.fct.2014.09.011","article-title":"Toxicity induced by F. poae-contaminated feed and the protective effect of Montmorillonite supplementation in broilers","volume":"74","author":"Yang","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1007\/s00216-011-5206-x","article-title":"Determination of zearalenone and its metabolites in endometrial cancer by coupled separation techniques","volume":"401","author":"Cendrowski","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1177\/0960327108099525","article-title":"A review of the toxic effects and mechanisms of action of fumonisin B1","volume":"27","author":"Savolainen","year":"2008","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.3748\/wjg.v19.i17.2587","article-title":"Mycotoxins are conventional and novel risk biomarkers for hepatocellular carcinoma","volume":"19","author":"Matsuda","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/jat.982","article-title":"Effects of rosmarinic acid against aflatoxin B1 and ochratoxin-A-induced cell damage in a human hepatoma cell line (Hep G2)","volume":"24","author":"Renzulli","year":"2004","journal-title":"J. Appl. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0278-6915(02)00045-5","article-title":"Genotoxic effects of ochratoxin A in human-derived hepatoma (HepG2) cells","volume":"40","author":"Ehrlich","year":"2002","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.tox.2008.08.020","article-title":"Different apoptotic pathways induced by zearalenone, T-2 toxin and ochratoxin A in human hepatoma cells","volume":"254","author":"Bouaziz","year":"2008","journal-title":"Toxicology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S0278-6915(03)00067-X","article-title":"New data on the occurrence of ochratoxin A in human sera from patients affected or not by renal diseases in Tunisia","volume":"41","author":"Grosso","year":"2003","journal-title":"Food Chem. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1080\/15287394.2012.707602","article-title":"Analysis of ochratoxin A blood levels in bladder cancer cases and healthy persons from Pakistan","volume":"75","author":"Aslam","year":"2012","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_41","first-page":"363","article-title":"Tissue zearalenone concentration in normal, hyperplastic and neoplastic human endometrium","volume":"69","author":"Tomaszewski","year":"1998","journal-title":"Ginekol. Pol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.fct.2018.06.037","article-title":"Prevalence and concentration of ochratoxin A, zearalenone, deoxynivalenol and total aflatoxin in cereal-based products: A systematic review and meta-analysis","volume":"118","author":"Fakhri","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"106940","DOI":"10.1016\/j.envint.2021.106940","article-title":"Elucidation of xenoestrogen metabolism by non-targeted, stable isotope-assisted mass spectrometry in breast cancer cells","volume":"158","author":"Flasch","year":"2022","journal-title":"Environ. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.3390\/toxins5081447","article-title":"Non-linear relationships between aflatoxin B1 levels and the biological response of monkey kidney vero cells","volume":"5","author":"Rasooly","year":"2013","journal-title":"Toxins"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0027-5107(99)00017-2","article-title":"DNA damage by mycotoxins","volume":"424","author":"Wang","year":"1999","journal-title":"Mutat. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/mc.22605","article-title":"Persistent phosphorylation at specific H3 serine residues involved in chemical carcinogen-induced cell transformation","volume":"56","author":"Zhu","year":"2017","journal-title":"Mol. Carcinog."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.fct.2018.03.012","article-title":"The G(2) phase arrest induced by sterigmatocystin is dependent on hMLH1- ERK\/p38-p53 pathway in human esophageal epithelium cells in vitro","volume":"115","author":"Cui","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ccell.2021.12.006","article-title":"Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma","volume":"40","author":"Dong","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.toxlet.2011.12.011","article-title":"ERK and p38 MAPK signaling pathways are involved in ochratoxin A-induced G2 phase arrest in human gastric epithelium cells","volume":"209","author":"Wang","year":"2012","journal-title":"Toxicol. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Sz\u0151ke, Z., Babarczi, B., M\u00e9zes, M., Lakatos, I., Po\u00f3r, M., Flisz\u00e1r-Ny\u00fal, E., Oldal, M., Cz\u00e9h, \u00c1., Bod\u00f3, K., and Nagy\u00e9ri, G. (2022). Analysis and Comparison of Rapid Methods for the Determination of Ochratoxin a Levels in Organs and Body Fluids Obtained from Exposed Mice. Toxins, 14.","DOI":"10.3390\/toxins14090634"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Falkauskas, R., Bakutis, B., Jovai\u0161ien\u0117, J., Vai\u010diulien\u0117, G., Gerulis, G., Kerzien\u0117, S., Jacevi\u010dien\u0117, I., Jacevi\u010dius, E., and Baliukonien\u0117, V. (2022). Zearalenone and Its Metabolites in Blood Serum, Urine, and Milk of Dairy Cows. Animals, 12.","DOI":"10.3390\/ani12131651"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/6\/236\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:47:06Z","timestamp":1760107626000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/16\/6\/236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,23]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["toxins16060236"],"URL":"https:\/\/doi.org\/10.3390\/toxins16060236","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,23]]}}}