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Genetic variation in the folate metabolic pathway and risk of childhood leukemia

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Genetic variation in the folate metabolic pathway and risk of childhood leukemia. / Lightfoot, Tracy J.; Johnston, W. Thomas; Painter, Daniel Edwin; Simpson, Jill; Roman, Eve; Skibola, Chris F.; Smith, Martyn T.; Allan, James M.; Taylor, G. Malcolm; United Kingdom Childhood Canc Stud.

In: Blood, Vol. 115, No. 19, 13.05.2010, p. 3923-3929.

Research output: Contribution to journalArticle

Harvard

Lightfoot, TJ, Johnston, WT, Painter, DE, Simpson, J, Roman, E, Skibola, CF, Smith, MT, Allan, JM, Taylor, GM & United Kingdom Childhood Canc Stud 2010, 'Genetic variation in the folate metabolic pathway and risk of childhood leukemia', Blood, vol. 115, no. 19, pp. 3923-3929. https://doi.org/10.1182/blood-2009-10-249722

APA

Lightfoot, T. J., Johnston, W. T., Painter, D. E., Simpson, J., Roman, E., Skibola, C. F., ... United Kingdom Childhood Canc Stud (2010). Genetic variation in the folate metabolic pathway and risk of childhood leukemia. Blood, 115(19), 3923-3929. https://doi.org/10.1182/blood-2009-10-249722

Vancouver

Lightfoot TJ, Johnston WT, Painter DE, Simpson J, Roman E, Skibola CF et al. Genetic variation in the folate metabolic pathway and risk of childhood leukemia. Blood. 2010 May 13;115(19):3923-3929. https://doi.org/10.1182/blood-2009-10-249722

Author

Lightfoot, Tracy J. ; Johnston, W. Thomas ; Painter, Daniel Edwin ; Simpson, Jill ; Roman, Eve ; Skibola, Chris F. ; Smith, Martyn T. ; Allan, James M. ; Taylor, G. Malcolm ; United Kingdom Childhood Canc Stud. / Genetic variation in the folate metabolic pathway and risk of childhood leukemia. In: Blood. 2010 ; Vol. 115, No. 19. pp. 3923-3929.

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@article{67d1d752275247928a0c59b3b2b5893c,
title = "Genetic variation in the folate metabolic pathway and risk of childhood leukemia",
abstract = "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)",
keywords = "ACUTE LYMPHOBLASTIC-LEUKEMIA, METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR, NON-HODGKIN-LYMPHOMA, ACUTE LYMPHOCYTIC-LEUKEMIA, NEURAL-TUBE DEFECTS, THYMIDYLATE-SYNTHASE, CHROMOSOME TRANSLOCATIONS, POLYMORPHISMS, SUSCEPTIBILITY, CANCER",
author = "Lightfoot, {Tracy J.} and Johnston, {W. Thomas} and Painter, {Daniel Edwin} and Jill Simpson and Eve Roman and Skibola, {Chris F.} and Smith, {Martyn T.} and Allan, {James M.} and Taylor, {G. Malcolm} and {United Kingdom Childhood Canc Stud}",
year = "2010",
month = "5",
day = "13",
doi = "10.1182/blood-2009-10-249722",
language = "English",
volume = "115",
pages = "3923--3929",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "19",

}

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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

VL - 115

SP - 3923

EP - 3929

JO - Blood

JF - Blood

SN - 0006-4971

IS - 19

ER -