title: MTHFR 677CC/1298CC genotypes are highly associated with chronic myelogenous leukemia: a case-control study in Korea.
abstract: Methylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in folate metabolism and DNA methylation. Studies on MTHFR polymorphism in leukemia have largely focused on the protective role of MTHFR polymorphism in acute lymphoblastic leukemia (ALL). We evaluated the C677T and A1298C polymorphisms using the TaqMan allelic discrimination assay in various malignancies. The study population included 115 subjects with chronic myelogenous leukemia (CML), 200 with acute myelogenous leukemia (AML), 196 with multiple myeloma (MM) and 434 healthy control subjects. The frequency of 1298CC was statistically significantly higher in subjects with CML than that of the controls (OR=5.12, 95% CI: 1.75-14.9, P-value=.003). Of note, the frequencies of 677CC/1298CC genotype were statistically significantly higher in subjects with CML, AML and MM than that of the controls (OR=8.8, 3.5, 3.83, P-value=.002, 0.036, 0.023, respectively). Our results demonstrate that the MTHFR 1298CC homozygote variant is strongly associated with an increased risk of CML, while MTHFR C677T does not significantly affect the risk of CML. Moreover, we demonstrated that MTHFR 677CC and 1298CC genotype might have combined effect on risk of CML, AML and MM and it is inferred that the A1298C may play a different role in carcinogenesis, depending on the types of organs involved, the types of disease entities and the genotype of C677T.
authors.affiliation: Department of Laboratory Medicine, Ewha Womans University College of Medicine, Seoul, South Korea.
authors.forename: Hee Won
authors.initials: HW
authors.lastname: Moon
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Kim
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: Oh
authors.forename: Hyun Chung
authors.initials: HC
authors.lastname: Min
authors.forename: Han Ik
authors.initials: HI
authors.lastname: Cho
authors.forename: Soo Mee
authors.initials: SM
authors.lastname: Bang
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Yoon
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D007723:Korea; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D017931:DNA Primers; D042965:Methylenetetrahydrofolate Reductase (NADPH2)