Genetic polymorphism of folate and methionine metabolizing enzymes and their susceptibility to malignant lymphoma.
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.
Habib
Emmad Ezzat
EE
The Department of Clinical Oncology, Cairo University Medical School, Clinical Pathology, Faculty of Medicine, Cairo University.
Aziz
Mona
M
Kotb
Magd
M
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
D005492:Folic Acid; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase