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Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia
- Source :
- Blood, 113(10), 2284-2289. AMER SOC HEMATOLOGY, Blood, 113(10), 2284-2289. American Society of Hematology, de Jonge, R, Tissing, W J, Hooijberg, J H, Jansen, G, Kaspers, G J L, Lindemans, J, Peters, G J & Pieters, R 2009, ' Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia ', Blood, vol. 113, no. 10, pp. 2284-2289 . https://doi.org/10.1182/blood-2008-07-165928
- Publication Year :
- 2009
- Publisher :
- American Society of Hematology, 2009.
-
Abstract
- 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.
- Subjects :
- Male
Reductase
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Biochemistry
Risk Factors
MALIGNANT-LYMPHOMA
Methionine synthase
Child
THYMIDYLATE SYNTHASE
Glycine Hydroxymethyltransferase
biology
Reverse Transcriptase Polymerase Chain Reaction
Hematology
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Ferredoxin-NADP Reductase
Child, Preschool
Female
NEURAL-TUBE DEFECTS
NON-HODGKIN-LYMPHOMA
Polymorphism, Restriction Fragment Length
medicine.medical_specialty
Adolescent
METHYLENETETRAHYDROFOLATE REDUCTASE GENE
SERINE HYDROXYMETHYLTRANSFERASE GENES
METABOLIZING GENES
Immunology
MTHFD1
Polymorphism, Single Nucleotide
Folic Acid
ACUTE LYMPHOCYTIC-LEUKEMIA
Internal medicine
Acute lymphocytic leukemia
medicine
Humans
Genetic Predisposition to Disease
Methylenetetrahydrofolate Reductase (NADPH2)
Infant, Newborn
Infant
Membrane Transport Proteins
Cell Biology
(Methionine synthase) reductase
medicine.disease
MTRR
COMMON MUTATION
Endocrinology
Methylenetetrahydrofolate dehydrogenase
Methylenetetrahydrofolate reductase
biology.protein
NICOTINAMIDE N-METHYLTRANSFERASE
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 113
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....f3e8adb34e418054c82682ad2001a45f
- Full Text :
- https://doi.org/10.1182/blood-2008-07-165928