{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T19:24:19Z","timestamp":1770146659366,"version":"3.49.0"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCMG (Czech Republic)","award":["LM2018132"],"award-info":[{"award-number":["LM2018132"]}]},{"name":"St. Anna Kinderkrebsforschung (Austria)","award":["not added"],"award-info":[{"award-number":["not added"]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology (Hungary)","award":["UNKP-19-3-IV (JC Sagi)"],"award-info":[{"award-number":["UNKP-19-3-IV (JC Sagi)"]}]},{"name":"Hungarian Paediatric Oncology Network (Hungary)","award":["07\/MGYH-MGYGYT\/2018"],"award-info":[{"award-number":["07\/MGYH-MGYGYT\/2018"]}]},{"name":"Swedish Childhood Cancer Fund (Sweden)","award":["KP2017-0010, TJ2020-0082, TJ2019-0031"],"award-info":[{"award-number":["KP2017-0010, TJ2020-0082, TJ2019-0031"]}]},{"name":"Danish Cancer Society (Denmark)","award":["R150-A10181"],"award-info":[{"award-number":["R150-A10181"]}]},{"name":"Danish Childhood Cancer Fund (Denmark)","award":["not added"],"award-info":[{"award-number":["not added"]}]},{"name":"National Research, Development and Innovation Office (NKFIH)","award":["Grants No. PD109200 (\u00c1F Semsei), PD134449 (A G\u00e9zsi) and K115861 (DJ Erd\u00e9lyi)"],"award-info":[{"award-number":["Grants No. PD109200 (\u00c1F Semsei), PD134449 (A G\u00e9zsi) and K115861 (DJ Erd\u00e9lyi)"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences (A G\u00e9zsi)","award":["not added"],"award-info":[{"award-number":["not added"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations\u2019 matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.<\/jats:p>","DOI":"10.3390\/cancers13102333","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T10:59:12Z","timestamp":1620817152000},"page":"2333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacogenetics of the Central Nervous System\u2014Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"13","author":[{"given":"Judit C.","family":"S\u00e1gi","sequence":"first","affiliation":[{"name":"Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1022-6356","authenticated-orcid":false,"given":"Andr\u00e1s","family":"G\u00e9zsi","sequence":"additional","affiliation":[{"name":"Department of Measurement and Information Systems, Budapest University of Technology and Economics, H-1111 Budapest, Hungary"},{"name":"MTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, Semmelweis University, H-1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1lint","family":"Egyed","sequence":"additional","affiliation":[{"name":"2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsuzsanna","family":"Jakab","sequence":"additional","affiliation":[{"name":"2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"No\u00e9mi","family":"Benedek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, P\u00e9cs University, H-7623 P\u00e9cs, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-6898","authenticated-orcid":false,"given":"Andishe","family":"Attarbaschi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, St. Anna Children\u2019s Hospital, Medical University of Vienna, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"K\u00f6hrer","sequence":"additional","affiliation":[{"name":"Renate Panzer-Gr\u00fcmayer: Leukemia Biology Group, Children\u2019s Cancer Research Institute, A-1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"Sipek","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, CZ-150 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Winkowska","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, CZ-150 06 Prague, Czech Republic"},{"name":"CLIP\u2014Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, CZ-150 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1639-7124","authenticated-orcid":false,"given":"Marketa","family":"Zaliova","sequence":"additional","affiliation":[{"name":"Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, CZ-150 06 Prague, Czech Republic"},{"name":"CLIP\u2014Childhood Leukemia Investigation Prague, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, CZ-150 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4210-0064","authenticated-orcid":false,"given":"Stavroula","family":"Anastasopoulou","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, S-17177 Stockholm, Sweden"},{"name":"Astrid Lindgren Children\u2019s Hospital, Karolinska University Hospital, S-14186 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin Ole","family":"Wolthers","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Rigshospitalet, DK-2100 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Ranta","sequence":"additional","affiliation":[{"name":"Childhood Cancer Research Unit, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet, S-17177 Stockholm, Sweden"},{"name":"Astrid Lindgren Children\u2019s Hospital, Karolinska University Hospital, S-14186 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6562-0778","authenticated-orcid":false,"given":"Csaba","family":"Szalai","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary"},{"name":"Central Laboratory, Heim P\u00e1l Children\u2019s Hospital, H-1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00e1bor T.","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8709-2459","authenticated-orcid":false,"given":"\u00c1gnes F.","family":"Semsei","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5544-9209","authenticated-orcid":false,"given":"D\u00e1niel J.","family":"Erd\u00e9lyi","sequence":"additional","affiliation":[{"name":"2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41591-019-0383-9","article-title":"Developmental origins and emerging therapeutic opportunities for childhood 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