title: Common gene polymorphisms in the metabolic folate and methylation pathway and the risk of acute lymphoblastic leukemia and non-Hodgkin's lymphoma in adults.
abstract: Folate and methionine metabolism is involved in DNA synthesis and methylation processes. Polymorphisms in the genes of folate metabolism enzymes have been associated with some forms of cancer. In a case-control study, we evaluated whether four common polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G), and methionine synthase reductase (MTRR A66G) genes may have a role in altering susceptibility to adult acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). We analyzed DNA of 120 adult ALL, 200 NHL, and 257 healthy control subjects. Individual carrying the MTHFR 677TT genotype showed a 3.6-fold decreased ALL risk [odds ratio (OR) 0.28, 95% confidence interval (95% CI) 0.12-0.72] than wild-types. Similarly, MS 2756GG individuals showed a 5.0-fold decreased ALL risk (OR 0.20, 95% CI 0.02-1.45) than wild-types. In combined results, subjects with the MTHFR 677CT/TT and MS 2756AG/GG genotypes revealed a 3.6-fold ALL risk reduction (OR 0.28, 95% CI 0.14-0.58) and those with the MTHFR 677TT and MTRR 66AG genotypes revealed a 4.2-fold ALL risk reduction (OR 0.24, 95% CI 0.06-0.81). Finally, those with the MS 2756AG/GG and MTRR 66AG/GG genotypes revealed a 2.2-fold ALL risk reduction (OR 0.45, 95% CI 0.10-0.85). Single analysis for NHL did not show any significant difference for all the polymorphisms investigated, but in the low-grade NHL subgroup, we found a 2.0-fold risk reduction for the MTRR 66GG homozygous genotype (OR 0.50, 95% CI 0.25-0.99), which was higher (OR 0.37, 95% CI 0.14-0.85) when analyzed in combination with MS 2756AA genotype. These data are in accordance with the hypothesis that polymorphisms in the genes for folate and methionine metabolism might play a greater role in the occurrence of ALL than NHL by influencing DNA synthesis and/or DNA methylation.
authors.affiliation: Department of Biomedical Sciences and Advanced Therapies, Center Study for Hemostasis and Thrombosis, University of Ferrara, C.so Giovecca 203, I-44100 Ferrara, Italy. d.gemmati@unife.it
authors.forename: Donato
authors.initials: D
authors.lastname: Gemmati
authors.forename: Alessia
authors.initials: A
authors.lastname: Ongaro
authors.forename: Gian L
authors.initials: GL
authors.lastname: Scapoli
authors.forename: Matteo
authors.initials: M
authors.lastname: Della Porta
authors.forename: Silvia
authors.initials: S
authors.lastname: Tognazzo
authors.forename: Maria L
authors.initials: ML
authors.lastname: Serino
authors.forename: Eros
authors.initials: E
authors.lastname: Di Bona
authors.forename: Francesco
authors.initials: F
authors.lastname: Rodeghiero
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gilli
authors.forename: Roberto
authors.initials: R
authors.lastname: Reverberi
authors.forename: Angelo
authors.initials: A
authors.lastname: Caruso
authors.forename: Michela
authors.initials: M
authors.lastname: Pasello
authors.forename: Agnese
authors.initials: A
authors.lastname: Pellati
authors.forename: Monica
authors.initials: M
authors.lastname: De Mattei
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*; D011336:Probability; D011379:Prognosis; D018570:Risk Assessment; D017678:Sex Distribution
chemical_list: C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase