Cancer Causes & Control

, Volume 27, Issue 7, pp 929–940 | Cite as

Maternal prenatal intake of one-carbon metabolism nutrients and risk of childhood leukemia

  • Amanda W. SingerEmail author
  • Steve Selvin
  • Gladys Block
  • Carla Golden
  • Suzan L. Carmichael
  • Catherine Metayer
Original paper



Folate, vitamins B12 and B6, riboflavin, and methionine are critical nutrients for the one-carbon metabolism cycle involved in DNA synthesis and epigenetic processes. We examined the association between maternal intake of these nutrients before pregnancy and risk of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in a matched case–control study.


Maternal dietary intake and vitamin supplement use in the year before pregnancy was assessed by food frequency questionnaire for 681 ALL cases, 103 AML cases, and 1076 controls. Principal component analysis was used to construct a variable representing combined nutrient intake, and conditional logistic regression estimated the odds ratio (OR) and 95% confidence interval (CI) for the association of ALL and AML with the principal component and each nutrient.


Higher maternal intake of one-carbon metabolism nutrients from food and supplements combined was associated with reduced risk of ALL (OR for one-unit change in the principal component = 0.91, CI 0.84–0.99) and possibly AML (OR for the principal component = 0.83, CI 0.66–1.04). When analyzed separately, intake of supplements high in these nutrients was associated with a reduced risk of ALL in children of Hispanic women only.


In conclusion, these data suggest that higher maternal intake of one-carbon metabolism nutrients may reduce risk of childhood leukemia.


Cancer risk Case/control Micronutrients Epidemiology Methyl donors 



This research was supported by National Institute of Environmental Health Sciences grants R01ES009137 and P-42-ES-04705-18 (University of California, Berkeley). We thank Semira Gonseth Nusslé and Joe Wiemels for helpful feedback on this work, and the staff of the California Childhood Leukemia Study for their contributions to this research. We are grateful to the families who participated in this study and the clinical investigators and their teams at the collaborating hospitals for their role in recruiting patients to this study: University of California, Davis, Medical Center (J. Ducore), University of California, San Francisco (M. Loh and K. Matthay), Children’s Hospital of Central California (V. Crouse), Lucile Packard Children’s Hospital (G Dahl), Children’s Hospital Oakland (J. Feusner), Kaiser Permanente Roseville (formerly Sacramento; K. Jolly and V. Kiley), Kaiser Permanente Santa Clara (C. Russo, A. Wong, and D. Taggar), Kaiser Permanente San Francisco (K. Leung), and Kaiser Permanente Oakland (D. Kronish and S. Month).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Amanda W. Singer
    • 1
    Email author
  • Steve Selvin
    • 1
  • Gladys Block
    • 1
  • Carla Golden
    • 2
  • Suzan L. Carmichael
    • 3
  • Catherine Metayer
    • 1
  1. 1.Division of Epidemiology, School of Public HealthUniversity of California, BerkeleyBerkeleyUSA
  2. 2.Children’s Hospital OaklandOaklandUSA
  3. 3.Division of Neonatology and Developmental Medicine, Department of PediatricsStanford University School of MedicineStanfordUSA

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