TY - JOUR
T1 - Genetic variation in the folate metabolic pathway and risk of childhood leukemia
AU - Lightfoot, Tracy J.
AU - Johnston, W. Thomas
AU - Painter, Daniel Edwin
AU - Simpson, Jill
AU - Roman, Eve
AU - Skibola, Chris F.
AU - Smith, Martyn T.
AU - Allan, James M.
AU - Taylor, G. Malcolm
AU - United Kingdom Childhood Canc Stud
PY - 2010/5/13
Y1 - 2010/5/13
N2 - Studies of childhood leukemia and the potential etiologic role of genetic variation in folate metabolism have produced conflicting findings and have often been based on small numbers. We investigated the association between polymorphisms in key folate metabolism enzymes (MTHFR 677 C > T, MTHFR 1298 A > C, SHMT1 1420 C > T, MTR 2756 A > G, TS 1494del6, and TS 28bp repeat) in 939 cases of childhood acute lymphoblastic leukemia (ALL) and 89 cases of acute myeloid leukemia (AML) recruited into the United Kingdom Childhood Cancer Study. We also examined the maternal genotypes of 752 of these cases. Data from 824 noncancer controls recruited were used for comparison. No evidence of an association with MTHFR 677 was observed for ALL or AML, either in children or their mothers. However, in children an increased risk of ALL (odds ratio [OR] = 1.88; 95% confidence interval [CI], 1.16-3.07; P = .010) and AML (OR = 2.74; 95% CI, 1.07-7.01; P = .036) was observed with the MTR 2756 GG genotype; the association was most pronounced for cases with the MLL translocation (OR = 4.90; 95% CI, 1.30-18.45; P = .019). These data suggest that genetic variation in methionine synthase could mediate risk of childhood leukemia, either via effects on DNA methylation or via effects on fetal growth and development. Blood. 2010; 115(19): 3923-3929)
AB - Studies of childhood leukemia and the potential etiologic role of genetic variation in folate metabolism have produced conflicting findings and have often been based on small numbers. We investigated the association between polymorphisms in key folate metabolism enzymes (MTHFR 677 C > T, MTHFR 1298 A > C, SHMT1 1420 C > T, MTR 2756 A > G, TS 1494del6, and TS 28bp repeat) in 939 cases of childhood acute lymphoblastic leukemia (ALL) and 89 cases of acute myeloid leukemia (AML) recruited into the United Kingdom Childhood Cancer Study. We also examined the maternal genotypes of 752 of these cases. Data from 824 noncancer controls recruited were used for comparison. No evidence of an association with MTHFR 677 was observed for ALL or AML, either in children or their mothers. However, in children an increased risk of ALL (odds ratio [OR] = 1.88; 95% confidence interval [CI], 1.16-3.07; P = .010) and AML (OR = 2.74; 95% CI, 1.07-7.01; P = .036) was observed with the MTR 2756 GG genotype; the association was most pronounced for cases with the MLL translocation (OR = 4.90; 95% CI, 1.30-18.45; P = .019). These data suggest that genetic variation in methionine synthase could mediate risk of childhood leukemia, either via effects on DNA methylation or via effects on fetal growth and development. Blood. 2010; 115(19): 3923-3929)
KW - ACUTE LYMPHOBLASTIC-LEUKEMIA
KW - METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR
KW - NON-HODGKIN-LYMPHOMA
KW - ACUTE LYMPHOCYTIC-LEUKEMIA
KW - NEURAL-TUBE DEFECTS
KW - THYMIDYLATE-SYNTHASE
KW - CHROMOSOME TRANSLOCATIONS
KW - POLYMORPHISMS
KW - SUSCEPTIBILITY
KW - CANCER
UR - http://www.scopus.com/inward/record.url?scp=77952611948&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-10-249722
DO - 10.1182/blood-2009-10-249722
M3 - Article
SN - 0006-4971
VL - 115
SP - 3923
EP - 3929
JO - Blood
JF - Blood
IS - 19
ER -