Cancer Causes & Control

, 22:1243

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

  • 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
Original paper

DOI: 10.1007/s10552-011-9795-7

Cite this article as:
Metayer, C., Scélo, G., Chokkalingam, A.P. et al. Cancer Causes Control (2011) 22: 1243. doi:10.1007/s10552-011-9795-7

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.

Keywords

Case–control studyChildrenDNA methylationFolateGenetic polymorphismsLeukemia

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Catherine Metayer
    • 1
  • Ghislaine Scélo
    • 3
  • Anand P. Chokkalingam
    • 2
  • Lisa F. Barcellos
    • 2
  • Melinda C. Aldrich
    • 4
  • Jeffrey S. Chang
    • 5
  • Neela Guha
    • 3
  • Kevin Y. Urayama
    • 3
  • Helen M. Hansen
    • 6
  • Gladys Block
    • 2
  • Vincent Kiley
    • 7
  • John K. Wiencke
    • 6
  • Joseph L. Wiemels
    • 6
  • Patricia A. Buffler
    • 2
  1. 1.School of Public HealthUniversity of California, BerkeleyBerkeleyUSA
  2. 2.School of Public HealthUniversity of California, BerkeleyBerkeleyUSA
  3. 3.International Agency for Research on CancerLyonFrance
  4. 4.Division of Epidemiology, Institute for Medicine and Public HealthVanderbilt UniversityVanderbiltUSA
  5. 5.National Institute of Cancer Research, National Health Research InstitutesTainanTaiwan
  6. 6.Departments of Neurological Surgery & Epidemiology and BiostatisticsUniversity of California, San FranciscoSan FranciscoUSA
  7. 7.Kaiser Permanente HospitalRosevilleUSA