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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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

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References

  1. Ross JA, Johnson KJ, Spector LG, Kersey JH (2011) Epidemiology of acute childhood leukemia. In: Reaman GH, Smith FO (eds) Childhood leukemia: a practical handbook. Springer, New York

    Google Scholar 

  2. Wiemels J (2012) Childhood acute leukemia. In: Dietert RR, Luebke RW (eds) Immunotoxicity, immune dysfunction, and chronic disease. Springer, New York

    Google Scholar 

  3. Greaves MF, Wiemels J (2003) Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 3(9):639–649. doi:10.1038/nrc1164

    Article  CAS  PubMed  Google Scholar 

  4. Wiemels JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, Saha V, Biondi A, Greaves MF (1999) Prenatal origin of acute lymphoblastic leukaemia in children. Lancet 354(9189):1499–1503

    Article  CAS  PubMed  Google Scholar 

  5. Locasale JW (2013) Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 13(8):572–583. doi:10.1038/nrc3557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shane B (2008) Folate and vitamin B12 metabolism: overview and interaction with riboflavin, vitamin B6, and polymorphisms. Food Nutr Bull 29(2 Suppl):S5–S16 discussion S17–S19

    Article  PubMed  Google Scholar 

  7. Stefanska B, Karlic H, Varga F, Fabianowska-Majewska K, Haslberger A (2012) Epigenetic mechanisms in anti-cancer actions of bioactive food components—the implications in cancer prevention. Br J Pharmacol 167(2):279–297. doi:10.1111/j.1476-5381.2012.02002.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shah MS, Davidson LA, Chapkin RS (2012) Mechanistic insights into the role of microRNAs in cancer: influence of nutrient crosstalk. Front Genet 3:305. doi:10.3389/fgene.2012.00305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fenech M (2001) The role of folic acid and Vitamin B12 in genomic stability of human cells. Mutat Res 475(1–2):57–67

    Article  CAS  PubMed  Google Scholar 

  10. Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31(1):27–36. doi:10.1093/carcin/bgp220

    Article  CAS  PubMed  Google Scholar 

  11. Wong NC, Ashley D, Chatterton Z, Parkinson-Bates M, Ng HK, Halemba MS, Kowalczyk A, Bedo J, Wang Q, Bell K, Algar E, Craig JM, Saffery R (2012) A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia. Epigenet Off J DNA Methylation Soc 7(6):535–541. doi:10.4161/epi.20193

    Article  CAS  Google Scholar 

  12. Blom HJ, Shaw GM, den Heijer M, Finnell RH (2006) Neural tube defects and folate: case far from closed. Nat Rev Neurosci 7(9):724–731. doi:10.1038/nrn1986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Thompson JR, Gerald PF, Willoughby ML, Armstrong BK (2001) Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukaemia in childhood: a case-control study. Lancet 358(9297):1935–1940. doi:10.1016/s0140-6736(01)06959-8

    Article  CAS  PubMed  Google Scholar 

  14. Amigou A, Rudant J, Orsi L, Goujon-Bellec S, Leverger G, Baruchel A, Bertrand Y, Nelken B, Plat G, Michel G, Haouy S, Chastagner P, Ducassou S, Rialland X, Hemon D, Clavel J (2012) Folic acid supplementation, MTHFR and MTRR polymorphisms, and the risk of childhood leukemia: the ESCALE study (SFCE). Cancer Causes Control 23(8):1265–1277. doi:10.1007/s10552-012-0004-0

    Article  PubMed  Google Scholar 

  15. Bailey HD, Miller M, Langridge A, de Klerk NH, van Bockxmeer FM, Attia J, Scott RJ, Armstrong BK, Milne E (2012) Maternal dietary intake of folate and vitamins b6 and B12 during pregnancy and the risk of childhood acute lymphoblastic leukemia. Nutr Cancer 64(7):1122–1130. doi:10.1080/01635581.2012.707278

    Article  CAS  PubMed  Google Scholar 

  16. Milne E, Royle JA, Miller M, Bower C, de Klerk NH, Bailey HD, van Bockxmeer F, Attia J, Scott RJ, Norris MD, Haber M, Thompson JR, Fritschi L, Marshall GM, Armstrong BK (2010) Maternal folate and other vitamin supplementation during pregnancy and risk of acute lymphoblastic leukemia in the offspring. Int J Cancer 126(11):2690–2699. doi:10.1002/ijc.24969

    CAS  PubMed  Google Scholar 

  17. Dockerty JD, Herbison P, Skegg DC, Elwood M (2007) Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study. BMC Public Health 7:136. doi:10.1186/1471-2458-7-136

    Article  PubMed  PubMed Central  Google Scholar 

  18. Schuz J, Weihkopf T, Kaatsch P (2007) Medication use during pregnancy and the risk of childhood cancer in the offspring. Eur J Pediatr 166(5):433–441. doi:10.1007/s00431-006-0401-z

    Article  PubMed  Google Scholar 

  19. Jensen CD, Block G, Buffler P, Ma X, Selvin S, Month S (2004) Maternal dietary risk factors in childhood acute lymphoblastic leukemia (United States). Cancer Causes Control 15(6):559–570. doi:10.1023/B:CACO.0000036161.98734.17

    Article  PubMed  Google Scholar 

  20. Kwan ML, Jensen CD, Block G, Hudes ML, Chu LW, Buffler PA (2009) Maternal diet and risk of childhood acute lymphoblastic leukemia. Public Health Rep 124(4):503–514

    PubMed  PubMed Central  Google Scholar 

  21. Metayer C, Scelo G, Chokkalingam AP, Barcellos LF, Aldrich MC, Chang JS, Guha N, Urayama KY, Hansen HM, Block G, Kiley V, Wiencke JK, Wiemels JL, Buffler PA (2011) Genetic variants in the folate pathway and risk of childhood acute lymphoblastic leukemia. Cancer Causes Control 22(9):1243–1258. doi:10.1007/s10552-011-9795-7

    Article  PubMed  PubMed Central  Google Scholar 

  22. Metayer C, Milne E, Dockerty JD, Clavel J, Pombo-de-Oliveira MS, Wesseling C, Spector LG, Schuz J, Petridou E, Ezzat S, Armstrong BK, Rudant J, Koifman S, Kaatsch P, Moschovi M, Rashed WM, Selvin S, McCauley K, Hung RJ, Kang AY, Infante-Rivard C (2014) Maternal supplementation with folic acid and other vitamins and risk of leukemia in offspring: a childhood leukemia international consortium study. Epidemiology (Cambridge, Mass) 25(6):811–822. doi:10.1097/EDE.0000000000000141

    Article  Google Scholar 

  23. Puumala SE, Ross JA, Aplenc R, Spector LG (2013) Epidemiology of childhood acute myeloid leukemia. Pediatr Blood Cancer 60(5):728–733. doi:10.1002/pbc.24464

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lim JY, Bhatia S, Robison LL, Yang JJ (2013) Genomics of racial and ethnic disparities in childhood acute lymphoblastic leukemia. Cancer. doi:10.1002/cncr.28531

    Google Scholar 

  25. Barrington-Trimis JL, Cockburn M, Metayer C, Gauderman WJ, Wiemels J, McKean-Cowdin R (2015) Rising rates of acute lymphoblastic leukemia in Hispanic children: trends in incidence from 1992 to 2011. Blood 125(19):3033–3034. doi:10.1182/blood-2015-03-634006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ma X, Buffler PA, Wiemels JL, Selvin S, Metayer C, Loh M, Does MB, Wiencke JK (2005) Ethnic difference in daycare attendance, early infections, and risk of childhood acute lymphoblastic leukemia. Cancer Epidemiol Biomark Prev Publ Am Asso Cancer Research Cosponsored Am Soc Prev Oncol 14(8):1928–1934. doi:10.1158/1055-9965.EPI-05-0115

    Article  Google Scholar 

  27. Francis SS, Selvin S, Metayer C, Wallace AD, Crouse V, Moore TB, Wiemels JL, Buffler PA (2014) Mode of delivery and risk of childhood leukemia. Cancer Epidemiol Biomark Prev Publ Am Asso Cancer Research Cosponsored Am Soc Prev Oncol 23(5):876–881. doi:10.1158/1055-9965.EPI-13-1098

    Article  Google Scholar 

  28. Urayama KY, Ma X, Selvin S, Metayer C, Chokkalingam AP, Wiemels JL, Does M, Chang J, Wong A, Trachtenberg E, Buffler PA (2011) Early life exposure to infections and risk of childhood acute lymphoblastic leukemia. Int J Cancer 128(7):1632–1643. doi:10.1002/ijc.25752

    Article  CAS  PubMed  Google Scholar 

  29. Xu H, Cheng C, Devidas M, Pei D, Fan Y, Yang W, Neale G, Scheet P, Burchard EG, Torgerson DG, Eng C, Dean M, Antillon F, Winick NJ, Martin PL, Willman CL, Camitta BM, Reaman GH, Carroll WL, Loh M, Evans WE, Pui CH, Hunger SP, Relling MV, Yang JJ (2012) ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia. J Clin Oncol Off J Am Soc Clin Oncol 30(7):751–757. doi:10.1200/JCO.2011.38.0345

    Article  CAS  Google Scholar 

  30. Walsh KM, Chokkalingam AP, Hsu LI, Metayer C, de Smith AJ, Jacobs DI, Dahl GV, Loh ML, Smirnov IV, Bartley K, Ma X, Wiencke JK, Barcellos LF, Wiemels JL, Buffler PA (2013) Associations between genome-wide native American ancestry, known risk alleles and B-cell ALL risk in Hispanic children. Leuk Off J Leuk Soc Am Leuk Res Fund UK. doi:10.1038/leu.2013.130

    Google Scholar 

  31. Walsh KM, de Smith AJ, Chokkalingam AP, Metayer C, Roberts W, Barcellos LF, Wiemels JL, Buffler PA (2013) GATA3 risk alleles are associated with ancestral components in Hispanic children with ALL. Blood 122(19):3385–3387. doi:10.1182/blood-2013-08-524124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kirkpatrick SI, Dodd KW, Reedy J, Krebs-Smith SM (2012) Income and race/ethnicity are associated with adherence to food-based dietary guidance among US adults and children. J Acad Nutr Diet 112(5):624–635. doi:10.1016/j.jand.2011.11.012 e626

    Article  PubMed  PubMed Central  Google Scholar 

  33. Ma X, Buffler PA, Layefsky M, Does MB, Reynolds P (2004) Control selection strategies in case-control studies of childhood diseases. Am J Epidemiol 159(10):915–921

    Article  PubMed  Google Scholar 

  34. Bartley K, Metayer C, Selvin S, Ducore J, Buffler P (2010) Diagnostic X-rays and risk of childhood leukaemia. Int J Epidemiol 39(6):1628–1637. doi:10.1093/ije/dyq162

    Article  PubMed  PubMed Central  Google Scholar 

  35. Suitor CW, Bailey LB (2000) Dietary folate equivalents: interpretation and application. J Am Diet Assoc 100(1):88–94. doi:10.1016/S0002-8223(00)00027-4

    Article  CAS  PubMed  Google Scholar 

  36. Dockerty JD, Draper G, Vincent T, Rowan SD, Bunch KJ (2001) Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers. Int J Epidemiol 30(6):1428–1437

    Article  CAS  PubMed  Google Scholar 

  37. Poole C, Greenland S, Luetters C, Kelsey JL, Mezei G (2006) Socioeconomic status and childhood leukaemia: a review. Int J Epidemiol 35(2):370–384. doi:10.1093/ije/dyi248

    Article  PubMed  Google Scholar 

  38. Hiza HA, Casavale KO, Guenther PM, Davis CA (2013) Diet quality of Americans differs by age, sex, race/ethnicity, income, and education level. J Acad Nutr Diet 113(2):297–306. doi:10.1016/j.jand.2012.08.011

    Article  PubMed  Google Scholar 

  39. Freedman LS, Schatzkin A, Midthune D, Kipnis V (2011) Dealing with dietary measurement error in nutritional cohort studies. J Natl Cancer Inst 103(14):1086–1092. doi:10.1093/jnci/djr189

    Article  PubMed  PubMed Central  Google Scholar 

  40. Willett WC, Howe GR, Kushi LH (1997) Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr 65(4 Suppl):1220S–1228S 1229S-1231S

    CAS  PubMed  Google Scholar 

  41. Halsted CH, Villanueva JA, Devlin AM, Chandler CJ (2002) Metabolic interactions of alcohol and folate. J Nutr 132(8 Suppl):2367S–2372S

    CAS  PubMed  Google Scholar 

  42. Mason JB, Choi SW (2005) Effects of alcohol on folate metabolism: implications for carcinogenesis. Alcohol 35(3):235–241. doi:10.1016/j.alcohol.2005.03.012

    Article  CAS  PubMed  Google Scholar 

  43. Petridou E, Ntouvelis E, Dessypris N, Terzidis A, Trichopoulos D, Childhood Hematology-Oncology G (2005) Maternal diet and acute lymphoblastic leukemia in young children. Cancer Epidemiol Biomark Prev Publ Am Asso Cancer Research Cosponsored Am Soc Prev Oncol 14(8):1935–1939. doi:10.1158/1055-9965.EPI-05-0090

    Article  Google Scholar 

  44. Palmer AC (2011) Nutritionally mediated programming of the developing immune system. Adv Nutr 2(5):377–395. doi:10.3945/an.111.000570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ramakrishnan U, Grant F, Goldenberg T, Zongrone A, Martorell R (2012) Effect of women’s nutrition before and during early pregnancy on maternal and infant outcomes: a systematic review. Paediatr Perinat Epidemiol 26(Suppl 1):285–301. doi:10.1111/j.1365-3016.2012.01281.x

    Article  PubMed  Google Scholar 

  46. Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, Lindemans J, Siebel C, Steegers EA, Slagboom PE, Heijmans BT (2009) Periconceptional maternal folic acid use of 400 microg per day is related to increased methylation of the IGF2 gene in the very young child. PLoS One 4(11):e7845. doi:10.1371/journal.pone.0007845

    Article  PubMed  PubMed Central  Google Scholar 

  47. Tamura T, Picciano MF (2006) Folate and human reproduction. Am J Clin Nutr 83(5):993–1016

    CAS  PubMed  Google Scholar 

  48. Crozier SR, Robinson SM, Godfrey KM, Cooper C, Inskip HM (2009) Women’s dietary patterns change little from before to during pregnancy. J Nutr 139(10):1956–1963. doi:10.3945/jn.109.109579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Rifas-Shiman SL, Rich-Edwards JW, Willett WC, Kleinman KP, Oken E, Gillman MW (2006) Changes in dietary intake from the first to the second trimester of pregnancy. Paediatr Perinat Epidemiol 20(1):35–42. doi:10.1111/j.1365-3016.2006.00691.x

    Article  PubMed  PubMed Central  Google Scholar 

  50. Nygard O, Refsum H, Ueland PM, Vollset SE (1998) Major lifestyle determinants of plasma total homocysteine distribution: the Hordaland Homocysteine Study. Am J Clin Nutr 67(2):263–270

    CAS  PubMed  Google Scholar 

  51. Jacques PF, Kalmbach R, Bagley PJ, Russo GT, Rogers G, Wilson PW, Rosenberg IH, Selhub J (2002) The relationship between riboflavin and plasma total homocysteine in the Framingham offspring cohort is influenced by folate status and the C677T transition in the methylenetetrahydrofolate reductase gene. J Nutr 132(2):283–288

    CAS  PubMed  Google Scholar 

  52. Gabriel HE, Crott JW, Ghandour H, Dallal GE, Choi SW, Keyes MK, Jang H, Liu Z, Nadeau M, Johnston A, Mager D, Mason JB (2006) Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults. Am J Clin Nutr 83(4):835–841

    CAS  PubMed  Google Scholar 

  53. Yang QH, Botto LD, Gallagher M, Friedman JM, Sanders CL, Koontz D, Nikolova S, Erickson JD, Steinberg K (2008) Prevalence and effects of gene-gene and gene-nutrient interactions on serum folate and serum total homocysteine concentrations in the United States: findings from the third National Health and Nutrition Examination Survey DNA Bank. Am J Clin Nutr 88(1):232–246

    CAS  PubMed  Google Scholar 

  54. Yang QH, Carter HK, Mulinare J, Berry RJ, Friedman JM, Erickson JD (2007) Race-ethnicity differences in folic acid intake in women of childbearing age in the United States after folic acid fortification: findings from the National Health and Nutrition Examination Survey, 2001–2002. Am J Clin Nutr 85(5):1409–1416

    CAS  PubMed  Google Scholar 

  55. Bailey RL, Dodd KW, Gahche JJ, Dwyer JT, McDowell MA, Yetley EA, Sempos CA, Burt VL, Radimer KL, Picciano MF (2010) Total folate and folic acid intake from foods and dietary supplements in the United States: 2003-2006. Am J Clin Nutr 91(1):231–237. doi:10.3945/ajcn.2009.28427

    Article  CAS  PubMed  Google Scholar 

  56. Solis C, Veenema K, Ivanov AA, Tran S, Li R, Wang W, Moriarty DJ, Maletz CV, Caudill MA (2008) Folate intake at RDA levels is inadequate for Mexican American men with the methylenetetrahydrofolate reductase 677TT genotype. J Nutr 138(1):67–72

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Robitaille J, Hamner HC, Cogswell ME, Yang Q (2009) Does the MTHFR 677C– > T variant affect the recommended dietary allowance for folate in the US population? Am J Clin Nutr 89(4):1269–1273. doi:10.3945/ajcn.2008.27282

    Article  CAS  PubMed  Google Scholar 

  58. Dowd JB, Aiello AE (2008) Did national folic acid fortification reduce socioeconomic and racial disparities in folate status in the US? Int J Epidemiol 37(5):1059–1066. doi:10.1093/ije/dyn066

    Article  PubMed  Google Scholar 

  59. Greenland S, Schwartzbaum JA, Finkle WD (2000) Problems due to small samples and sparse data in conditional logistic regression analysis. Am J Epidemiol 151(5):531–539

    Article  CAS  PubMed  Google Scholar 

  60. Bunin GR, Gyllstrom ME, Brown JE, Kahn EB, Kushi LH (2001) Recall of diet during a past pregnancy. Am J Epidemiol 154(12):1136–1142

    Article  CAS  PubMed  Google Scholar 

  61. Willett WC (2013) Nutritional Epidemiology, vol 40. Monographs in Epidemiology and Biostatistics Oxford University Press, New York

  62. Byers T (2001) Food frequency dietary assessment: how bad is good enough? Am J Epidemiol 154(12):1087–1088

    Article  CAS  PubMed  Google Scholar 

  63. Drews CD, Kraus JF, Greenland S (1990) Recall bias in a case-control study of sudden infant death syndrome. Int J Epidemiol 19(2):405–411

    Article  CAS  PubMed  Google Scholar 

  64. Infante-Rivard C, Jacques L (2000) Empirical study of parental recall bias. Am J Epidemiol 152(5):480–486

    Article  CAS  PubMed  Google Scholar 

  65. Kwan ML, Metayer C, Crouse V, Buffler PA (2007) Maternal illness and drug/medication use during the period surrounding pregnancy and risk of childhood leukemia among offspring. Am J Epidemiol 165(1):27–35. doi:10.1093/aje/kwj336

    Article  PubMed  Google Scholar 

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Acknowledgments

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).

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Authors and Affiliations

  1. Division of Epidemiology, School of Public Health, University of California, Berkeley, 1995 University Avenue, Suite 460, Berkeley, CA, 94704, USA

    Amanda W. Singer, Steve Selvin, Gladys Block & Catherine Metayer

  2. Children’s Hospital Oakland, Oakland, CA, USA

    Carla Golden

  3. Division of Neonatology and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    Suzan L. Carmichael

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  1. Amanda W. Singer
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Correspondence to Amanda W. Singer.

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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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Singer, A.W., Selvin, S., Block, G. et al. Maternal prenatal intake of one-carbon metabolism nutrients and risk of childhood leukemia. Cancer Causes Control 27, 929–940 (2016). https://doi.org/10.1007/s10552-016-0773-y

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