Folate metabolism and risk of childhood acute lymphoblastic leukemia: a genetic pathway analysis from the Childhood Cancer and Leukemia International Consortium

Details

• Alternative Title:
  Cancer Epidemiol Biomarkers Prev
• Personal Author:
  Metayer, Catherine ; Spector, Logan G. ; Scheurer, Michael E. ; Jeon, Soyoung ; Scott, Rodney J. ; Takagi, Masatoshi ; Clavel, Jacqueline ; Manabe, Atsushi ; Ma, Xiaomei ; Hailu, Elleni M. ; Lupo, Philip J. ; Urayama, Kevin Y. ; Bonaventure, Audrey ; Kato, Motohiro ; Meirhaeghe, Aline ; Chiang, Charleston W.K. ; Morimoto, Libby M. ; Wiemels, Joseph L.
• Description:
  Background:
  
  Prenatal folate supplementation has been consistently associated with a reduced risk of childhood lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity, and led to inconclusive results.
  
  Methods:
  
  We evaluated whether ~2,900 single nucleotide polymorphisms (SNPs) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control-studies in the Childhood Cancer and Leukemia International Consortium (n=9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data, and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software.
  
  Results:
  
  None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni p-value of 5×10−6 and less stringent p-value of 3.5×10−5 accounting for the number of “independent” SNPs). None of the 10 top (non-significant) SNPs and corresponding genes overlapped across ancestry groups.
  
  Conclusion:
  
  This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups.
  
  Impact:
  
  Genetic variants in the folate pathway alone do not appear to substantially influence childhood ALL risk. Other mechanisms such as gene-folate interaction, DNA methylation or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.
  
  
• Subjects:
  Case-Control Studies Child Child, Preschool Female Folic Acid Genetic Predisposition To Disease Genome-Wide Association Study Humans Male Polymorphism, Single Nucleotide Precursor Cell Lymphoblastic Leukemia-Lymphoma Risk Factors

  More +
• Keywords:
  Childhood Leukemia Folate Genes Meta-analysis
• Source:
  Cancer Epidemiol Biomarkers Prev. 33(9):1248-1252
• Pubmed ID:
  38904462
• Pubmed Central ID:
  PMC11369612
• Document Type:
  Journal Article
• Funding:
  R24 ES028524/ES/NIEHS NIH HHSUnited States/ ; HHSN261201000140C/CA/NCI NIH HHSUnited States/ ; HHSN261201000035C/CA/NCI NIH HHSUnited States/ ; R01 CA155461/CA/NCI NIH HHSUnited States/ ; HHSN261201000035I/CA/NCI NIH HHSUnited States/ ; HHSN261201000034C/CA/NCI NIH HHSUnited States/ ; R01 AG033067/AG/NIA NIH HHSUnited States/ ; 19-308/CHILDREN with CANCER UK/ ; P42 ES004705/ES/NIEHS NIH HHSUnited States/ ; U58 DP003862/DP/NCCDPHP CDC HHSUnited States/ ; WT_/Wellcome TrustUnited Kingdom/ ; R01 ES009137/ES/NIEHS NIH HHSUnited States/
• Volume:
  33
• Issue:
  9
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:a8f3aeeaed292250960977740b0942cef10fe4cd68c74b16356fa00d06a51c46976a9bce0d81d331759d3212ec37ea8569ccb86eaa1f6ea076b4b0119419e189
• Download URL:
  https://stacks.cdc.gov/view/cdc/160715/cdc_160715_DS1.pdf
• File Type:
  [PDF - 98.22 KB ]