SEARCH:   Advanced

Blood, 5 March 2009, Vol. 113, No. 10, pp. 2284-2289. Prepublished online as a Blood First Edition Paper on November 19, 2008; DOI 10.1182/blood-2008-07-165928. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-165928v1 113/10/2284    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by de Jonge, R. Articles by Pieters, R. Search for Related Content PubMed PubMed Citation Articles by de Jonge, R. Articles by Pieters, R. Related Collections Free Research Articles Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia Robert de Jonge1, Wim J. E. Tissing2,3, Jan Hendrik Hooijberg4, Gerrit Jansen5, Gertjan J. L. Kaspers4, Jan Lindemans1, Godefridus J. Peters6, and Rob Pieters2 1 Clinical Chemistry, Erasmus University Medical Center (Erasmus MC), Rotterdam; 2 Pediatric Oncology/Hematology, Erasmus MC–Sophia, Rotterdam; 3 Pediatric Oncology/Hematology, Beatrix Children's Hospital, University of Groningen and University Medical Center Groningen, Groningen; 4 Pediatric Oncology/Hematology, Vrije Universiteit (VU) University Medical Center, Amsterdam; 5 Rheumatology, VU University Medical Center, Amsterdam; and 6 Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands Polymorphisms in folate pathway genes may influence the susceptibility to acute lymphoblastic leukemia (ALL). DNA was isolated from 245 pediatric ALL patients (cases) and from 500 blood bank donors (controls). Polymorphisms in methylene-tetrahydrofolate reductase (MTHFR 677C>T, 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), nicotinamide N-methyltransferase (NNMT IVS –151C>T), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC1 80G>A) were detected. In ALL patients, an increased occurrence was observed of the RFC1 80AA variant (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.2; P = .002) and the RFC1 80A allele (OR = 1.5; 95% CI, 1.1-2.1; P = .02). Likewise, the NNMT IVS –151TT genotype showed a 2.2-fold increased ALL risk (OR = 2.2; 95% CI, 1.1-4.6; P = .04). A 1.4-fold reduction in ALL risk was observed for (heterozygous or homozygous) carriers of the TS 2R allele and the MTHFR 677T allele (OR = 0.7; 95% CI, 0.5-1.0; P < .05). Furthermore, interactions between NNMT and MTHFR 677C>T and RFC1 were observed. NNMT IVS –151CC/MTHFR 677CT + TT patients exhibited a 2-fold reduction in ALL risk whereas RFC1 80AA/NNMT IVS –151CT + TT subjects had a 4.2-fold increase in ALL risk (P = .001). For the first time, we associate the RFC1 80G>A and NNMT IVS –151C>T variants to an increased ALL susceptibility. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020