title: Genetic polymorphism of folate and methionine metabolizing enzymes and their susceptibility to malignant lymphoma.
abstract: BACKGROUND
  Folate and methionine metabolism is involved in DNA synthesis and methylation. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylene-tetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms MTHFR 677 C-->T and MTHFR 1298 A-->C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5, 10- methylene-tetrahydrofolate and results in a reduced incidence of DNA double strand breakage. The MS 2756 A-->G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA.
  
  
  METHODS
  To test this hypothesis, genetic polymorphisms in the folate metabolic pathway were investigated using the DNA from a case-control study on 31 patients having malignant lymphoma from the Oncology Outpatient Clinic of the New Children's Hospital, Cairo University and 30 controls who were actually normal children attending for vaccination to the same hospital.
  
  
  RESULTS
  We found that there is a higher susceptibility with the MTHFR 677CC and MTHFR 1298 AA genotypes (OR=4.3, 95% CI 1.12-16). When those harbor at least one variant allele in either polymorphism of MTHFR they were defined as reference. For the MS 2756 AG genotype polymorphism there was also a higher susceptibility to developing malignant lymphoma (OR=2.6; 95% CI 1.1- 6.4).
  
  
  CONCLUSIONS
  Results suggest that folate and methionine metabolism may play an important role in the pathogenesis of malignant lymphoma. Further studies to confirm this association and detailed biologic mechanisms are now required.
authors.affiliation: The Department of Clinical Oncology, Cairo University Medical School, Clinical Pathology, Faculty of Medicine, Cairo University.
authors.forename: Emmad Ezzat
authors.initials: EE
authors.lastname: Habib
authors.forename: Mona
authors.initials: M
authors.lastname: Aziz
authors.forename: Magd
authors.initials: M
authors.lastname: Kotb
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000378:metabolism*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D005492:Folic Acid; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase