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Cancer Causes & Control
Published in: Cancer Causes & Control 9/2011

01-09-2011 | Original paper

Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia

Authors: Catherine Metayer, Ghislaine Scélo, Anand P. Chokkalingam, Lisa F. Barcellos, Melinda C. Aldrich, Jeffrey S. Chang, Neela Guha, Kevin Y. Urayama, Helen M. Hansen, Gladys Block, Vincent Kiley, John K. Wiencke, Joseph L. Wiemels, Patricia A. Buffler

Published in: Cancer Causes & Control | Issue 9/2011

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Abstract

Objective

Folate is involved in the one-carbon metabolism that plays an essential role in the synthesis, repair, and methylation of DNA. We examined whether child’s germline genetic variation in the folate pathway is associated with childhood acute lymphoblastic leukemia (ALL), and whether periconception maternal folate and alcohol intake modify the risk.

Methods

Seventy-six single nucleotide polymorphisms (SNPs), including 66 haplotype-tagging SNPs in 10 genes (CBS, DHFR, FOLH1, MTHFD1, MTHFR, MTR, MTRR, SHMT1, SLC19A1, and TYMS), were genotyped in 377 ALL cases and 448 controls. Log-additive associations between genotypes and ALL risk were adjusted for age, sex, Hispanic ethnicity (when appropriate), and maternal race.

Results

Single and haplotype SNPs analyses showed statistically significant associations between SNPs located in (or adjacent to) CBS, MTRR, TYMS/ENOFS, and childhood ALL. Many regions of CBS were associated with childhood ALL in Hispanics and non-Hispanics (p < 0.01). Levels of maternal folate intake modified associations with SNPs in CBS, MTRR, and TYMS.

Conclusion

Our data suggest the importance of genetic variability in the folate pathway and childhood ALL risk.
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Metadata
Title
Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia
Authors
Catherine Metayer
Ghislaine Scélo
Anand P. Chokkalingam
Lisa F. Barcellos
Melinda C. Aldrich
Jeffrey S. Chang
Neela Guha
Kevin Y. Urayama
Helen M. Hansen
Gladys Block
Vincent Kiley
John K. Wiencke
Joseph L. Wiemels
Patricia A. Buffler
Publication date
01-09-2011
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 9/2011
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-011-9795-7

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