title: MTHFR C677T polymorphism: association with lymphoid neoplasm and effect on methotrexate therapy.
abstract: The aim of this study was to detect the possible role of methylene tetrahydrofolate reductase gene polymorphism (MTHFR C677T) in the pathogenesis of lymphoid neoplasms and to investigate the influence of this polymorphism on methotrexate toxicity in adult ALL patients treated with methotrexate maintenance therapy. There was a statistically significant increase in the risk of non-Hodgkin lymphoma in patients with CT genotype (OR, 2.9; 95% CI, 1.3-6.3; P = 0.007) and combined CT + TT genotype (OR, 3.2; 95% CI, 1.5-6.6; P = 0.006). While no significant association was found between this polymorphism and ALL risk. The patients with ALL treated with methotrexate during maintenance therapy were observed for signs of toxicity. MTHFR 677C>T polymorphism (CT + TT) was significantly overrepresented among cases with hepatic toxicity (OR = 15.6; 95% CI, 2.6-81.3; P = 0.001). In addition, they were overrepresented among cases with mucositis, anemia, thrombocytopenia, and leukopenia. However, it did not reach statistical significance level. Further studies on larger number of subjects are necessary. Additional studies on the role of MTHFR gene polymorphism with environment (folate intake) interaction are needed to confirm the role of these genetic polymorphisms.
authors.affiliation: Clinical Pathology Department, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
authors.forename: Mona W
authors.initials: MW
authors.lastname: Ayad
authors.forename: Amel A
authors.initials: AA
authors.lastname: El Naggar
authors.forename: Mostafa
authors.initials: M
authors.lastname: El Naggar
mesh_terms: D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D017931:DNA Primers; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate
keywords: MTHFR 677C>T; acute lymphoblastic leukemia; non-Hodgkin lymphoma