title: Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies.
abstract: Several genetic polymorphisms in the genes coding folate-metabolizing enzymes have been associated with susceptibility to hematology malignancies. We conducted a Korean population-based case-control study to examine the relationship between the polymorphisms of folate-metabolizing enzymes and the risk of AML (acute myelogenous leukemia), CML (chronic myelogenous leukemia), MDS (myelodyspastic syndrome), and ALL (acute lymphoblastc leukemia). The MTHFR 677TT genotype was associated with an increased risk for ALL (odds ratios (OR)=1.77; 95% confidence intervals (CI)=1.02-3.09, p=.044). The MTRR 66 AG genotype was associated with an increased risk for MDS (OR=1.59; 1.06-2.38, p=.026) and the MTRR 66 GG genotype was associated with increased risk for AML (OR=1.51; 1.03-2.23, p=.037). The TYMS 2R3R genotype was associated with a decreased risk for AML (OR=0.76; 0.60-0.96, p=.022). The TYMS hap3 (2R-6bp) and hap4 (2R-0bp) were associated with decreased risk (OR=0.69; 0.53-0.90, p=.006) and increased risk (OR=1.65; 1.20-2.27, p=.002), respectively for AML. Hap C (677T-1298A) was associated with an increased risk (OR=1.40; 1.02-1.92, p=.04) for ALL. The risk for ALL appears to be associated with the MTHFR 677 polymorphism. The results are supportive of a risk modification by folate polymorphisms in several hematologic malignancies in Korea. The pattern of results suggests that MDS was associated with the DNA methylation status and the risk for AML was associated with both the DNA synthesis and DNA methylation status.
authors.affiliation: Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea.
authors.forename: Hee Nam
authors.initials: HN
authors.lastname: Kim
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Lee
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Shin
authors.forename: Kyeong-Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Jin-Su
authors.initials: JS
authors.lastname: Choi
authors.forename: Moo Rim
authors.initials: MR
authors.lastname: Park
authors.forename: Deog Yeon
authors.initials: DY
authors.lastname: Jo
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Won
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Kwak
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D005838:Genotype; D019337:Hematologic Neoplasms / Q000201:enzymology*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)