{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T10:13:33Z","timestamp":1771668813601,"version":"3.50.1"},"reference-count":135,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives:\u00a0MTHFR gene polymorphisms (677C&gt;T and 1298A&gt;C) correlate with various types of cancer across all age groups; however, a small number of studies have included solely children and adolescents. The aim of this systematic review and meta-analysis was to present and synthesize all the available evidence on the association between MTHFR gene polymorphisms and the incidence of all types of cancer in children and adolescences. Methods: After a systematic search of all of the available data, original case\u2013control studies involving children or adolescents with a confirmed diagnosis of any type of cancer and a molecular genetic test of MTHFR gene polymorphisms were included. Results: A total of 53 original studies in children and adolescents with cancer were included in the systematic review. Among these, 40 studies reviewed children and adolescents with Acute Lymphoblastic Leukemia (ALL), 4 those with Acute Myeloblastic Leukemia (AML), 8 those with central nervous system (CNS) tumors and 3 those with other types of cancer. Children and adolescents with ALL had less frequent T allele sequences (CT and TT variations) of the 677C&gt;T polymorphism compared to a healthy population (OR: 0.85; CI: 0.80\u20130.91; p &lt; 0.00001). Concerning the 1298A&gt;C polymorphism, the C allele sequences (AC and CC) did not present a statistically significant difference in frequency compared to a healthy population (OR: 1.01; CI: 0.95\u20131.08; p = 0.69). Conclusions: Children and adolescents with ALL appeared to have the T allele sequences of the 677C&gt;T polymorphism of the MTHFR gene less frequently compared to a healthy population.<\/jats:p>","DOI":"10.3390\/children12010108","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T10:27:58Z","timestamp":1737109678000},"page":"108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MTHFR Gene Polymorphisms and Cancer Risk in Children and Adolescents: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0490-9196","authenticated-orcid":false,"given":"Savvas","family":"Kolanis","sequence":"first","affiliation":[{"name":"2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-4471","authenticated-orcid":false,"given":"Eleni P.","family":"Kotanidou","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliki Rengina","family":"Tsinopoulou","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-0610","authenticated-orcid":false,"given":"Elisavet","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Laboratory of Biological Chemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7535-2970","authenticated-orcid":false,"given":"Emmanuel","family":"Hatzipantelis","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liana","family":"Fidani","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece"},{"name":"Laboratory of Medical Biology-Genetics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-3893","authenticated-orcid":false,"given":"Assimina","family":"Galli-Tsinopoulou","sequence":"additional","affiliation":[{"name":"2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e20240215","DOI":"10.1590\/1806-9282.20240215","article-title":"MTHFR Genetic Testing: Is There a Clinical Utility?","volume":"70","author":"Planello","year":"2024","journal-title":"Rev. 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