Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia |
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| Authors: | Catherine Metayer Ghislaine Sc��lo 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 |
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| Affiliation: | School of Public Health, University of California, Berkeley, 1995 University Avenue, Suite 460, Berkeley, CA 94704-7392, USA. cmetayer@berkeley.edu |
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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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