{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T12:25:58Z","timestamp":1754396758577},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T00:00:00Z","timestamp":1384560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":654,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2014,8]]},"abstract":"Summary<\/jats:title>Introduction<\/jats:title>The association between the risk of acute lymphoblastic leukemia (ALL<\/jats:styled-content>) in children and enzymes involved in the folate metabolism has been under investigation lately. The reduced folate carrier gene (RFC<\/jats:styled-content><\/jats:italic>) encodes reduced folate carrier, a protein that transports into the cell both folate and methotrexate, a commonly used chemotherapeutic drug, has been proved polymorphic at position 80 (G\u2192A). The role of this polymorphism in childhood ALL<\/jats:styled-content> and its interaction with other enzymes of the folate metabolic pathway, including MTHFR<\/jats:styled-content>, has been examined in different populations with diverse results.<\/jats:p><\/jats:sec>Methods<\/jats:title>In the present case\u2013control study, 35 children with ALL<\/jats:styled-content> and 48 healthy adult blood donors, all originating from the island of C<\/jats:styled-content>rete (G<\/jats:styled-content>reece), were screened for the presence of the RFC<\/jats:styled-content> G80A<\/jats:italic> polymorphism, using PCR<\/jats:styled-content>\/RFLP<\/jats:styled-content> techniques. The effect on ALL<\/jats:styled-content> risk and methotrexate\u2010induced toxicities, along with the role of gene\u2013gene interactions in our population, were examined.<\/jats:p><\/jats:sec>Results<\/jats:title>No significant association was observed between the RFC<\/jats:styled-content> G80A<\/jats:italic> genotypes and either the development of ALL<\/jats:styled-content> or the presence of adverse events. However, a significant association was detected between the MTHFR<\/jats:styled-content> A1298C\/ RFC<\/jats:styled-content> G80A<\/jats:italic> genotype and a nonpredisposition for ALL<\/jats:styled-content> (P\u00a0=\u00a0<\/jats:italic>0.035).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This study suggests that gene\u2013gene interactions in childhood ALL<\/jats:styled-content> may be of prognostic value in our population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.12160","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T06:14:38Z","timestamp":1384582478000},"page":"425-430","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Effect of RFC<\/scp> G80A P<\/scp>olymorphism in C<\/scp>retan children with acute lymphoblastic leukemia and its interaction with MTHFR<\/scp> C677T and A1298C polymorphisms"],"prefix":"10.1111","volume":"36","author":[{"given":"N. V.","family":"Karathanasis","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology\u2010Oncology University Hospital of Heraklion University of Crete Heraklion Crete Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Stiakaki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\u2010Oncology University Hospital of Heraklion University of Crete Heraklion Crete Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. \u039d.","family":"Goulielmos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Section of Molecular Medicine and Human Genetics Medical School University Of Crete Heraklion Crete Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kalmanti","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology\u2010Oncology University Hospital of Heraklion University of Crete Heraklion Crete Greece"},{"name":"Department of Pediatrics University Hospital of Heraklion University of Crete Heraklion Crete Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,11,16]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052603"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.061408298"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21825"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3034"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.10.3832"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2005.08.008"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1998.2714"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402428"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.tpj.6500224"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2010.0083"},{"key":"e_1_2_6_12_1","unstructured":"Common Terminology Criteria for Adverse Events v4.0 (CTCAE). 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