Association between polymorphisms of folate-metabolizing enzymes and hematological malignancies.
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.
Kim
Hee Nam
HN
Genome Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanamdo, Republic of Korea.
Kim
Yeo-Kyeoung
YK
Lee
Il-Kwon
IK
Yang
Deok-Hwan
DH
Lee
Je-Jung
JJ
Shin
Min-Ho
MH
Park
Kyeong-Soo
KS
Choi
Jin-Su
JS
Park
Moo Rim
MR
Jo
Deog Yeon
DY
Won
Jong Ho
JH
Kwak
Jae-Yong
JY
Kim
Hyeoung-Joon
HJ
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
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)