Skip to main content

Advertisement

Log in

Paternal intake of folate and vitamins B6 and B12 before conception and risk of childhood acute lymphoblastic leukemia

  • Original paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

We investigated whether paternal dietary intake of folate before conception is associated with the risk of childhood acute lymphoblastic leukemia (ALL) in a nationwide case–control study.

Methods

Data on dietary folate intake during the 6 months before the child’s conception were collected from 285 case fathers and 595 control fathers using a dietary questionnaire. Nutrient intake was quantified using a customized computer software package based on Australian food composition databases. Data on folate intake were analyzed using unconditional logistic regression, adjusting for study-matching variables, total energy, and potentially confounding variables. In a subset of 229 cases and 420 controls, data on vitamin B6 and vitamin B12 intake were also analyzed.

Results

No consistent associations were seen with paternal dietary intake of folate or vitamin B6. Higher levels of paternal dietary vitamin B12 were appeared to be associated with an increased risk of childhood ALL, with those in the highest tertile of consumption having an OR of 1.51 (0.97, 2.36). The use of supplements containing folate and vitamins B6 or B12 was rare.

Conclusions

We did not find any biologically plausible evidence that paternal nutrition in the period leading up to conception was associated with childhood ALL. Our finding for vitamin B12 may be a chance finding, given the number of analyses performed, or be attributable to participation bias because parents with a tertiary education had the lowest level of B12 intake and tertiary education was more common among control than case parents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

ALL:

Acute lymphoblastic leukemia

Aus-ALL:

Australian Study of Causes of Acute Lymphoblastic Leukaemia in Children

CI:

Confidence interval

DFE:

Dietary folate equivalents

FFQ:

Food frequency questionnaire

OR:

Odds ratio

RDD:

Random digit dialling

References

  1. Ross JA (1998) Maternal diet and infant leukemia: a role for DNA topoisomerase II inhibitors? Int J Cancer Suppl 11:26–28

    Article  CAS  PubMed  Google Scholar 

  2. Spector LG, Xie Y, Robison LL et al (2005) Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children’s oncology group. Cancer Epidemiol Biomarkers Prev 14:651–655

    Article  CAS  PubMed  Google Scholar 

  3. Petridou E, Koussouri M, Toupadaki N et al (1998) Diet during pregnancy and the risk of cerebral palsy. Br J Nutr 79:407–412

    Article  CAS  PubMed  Google Scholar 

  4. 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 15:559–570

    Article  PubMed  Google Scholar 

  5. Selhub J (2002) Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J Nutr Health Aging 6:39–42

    CAS  PubMed  Google Scholar 

  6. Goh YI, Bollano E, Einarson TR, Koren G (2007) Prenatal multivitamin supplementation and rates of pediatric cancers: a meta-analysis. Clin Pharmacol Ther 81:685–691

    Article  CAS  PubMed  Google Scholar 

  7. Schuz J, Weihkopf T, Kaatsch P (2007) Medication use during pregnancy and the risk of childhood cancer in the offspring. Eur J Pediatr 166:433–441

    Article  PubMed  Google Scholar 

  8. 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 358:1935–1940

    Article  CAS  PubMed  Google Scholar 

  9. Wen WQ, Shu XO, Potter JD et al (2002) Parental medication use and risk of childhood acute lymphoblastic leukemia. Cancer 95:1786–1794

    Article  PubMed  Google Scholar 

  10. Mayr CA, Woodall AA, Ames BN (2001) DNA damage to sperm from micronutrient deficiency may increase the risk of defects and cancer in offspring. In: Bendich A, Declebaum RJ (eds) Preventative medicine; the comprehensive guide for health professionals. Humama Press, Totowa, pp 373–386

    Google Scholar 

  11. Boxmeer JC, Smit M, Utomo E et al (2009) Low folate in seminal plasma is associated with increased sperm DNA damage. Fertil Steril 92:548–556

    Article  CAS  PubMed  Google Scholar 

  12. Young SS, Eskenazi B, Marchetti FM, Block G, Wyrobek AJ (2008) The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Hum Reprod 23:1014–1022

    Article  CAS  PubMed  Google Scholar 

  13. Kim YI (1999) Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem 10:66–88

    Article  CAS  PubMed  Google Scholar 

  14. Bailey HD, Milne E, de Klerk N et al (2010) Representativeness of child controls recruited by random digit dialling. Paediatr Perinat Epidemiol 24:293–302

    Article  PubMed  Google Scholar 

  15. Bailey HD, Miller M, Langridge A et al (2012) Maternal dietary intake of folate and vitamins B6 and B12 during pregnancy and the risk of childhood acute lymphoblastic leukemia. Nutr Cancer 64:1122–1130

    Article  CAS  PubMed  Google Scholar 

  16. Bunin GR, Li Y, Ganguly A, Meadows AT, Tseng M (2013) Parental nutrient intake and risk of retinoblastoma resulting from new germline RB1 mutation. Cancer Causes Control 24:343–355

    Article  PubMed Central  PubMed  Google Scholar 

  17. Lassale C, Guilbert C, Keogh J, Syrette J, Lange K, Cox DN (2009) Estimating food intakes in Australia: validation of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) food frequency questionnaire against weighed dietary intakes. J Hum Nutr Diet 22:559–566

    Article  CAS  PubMed  Google Scholar 

  18. Food Standards Australia New Zealand (2007) AUSNUT 2007

  19. Food Standards Australia New Zealand (2011) NUTTAB 2010: Australian Food Composition Tables

  20. Bailey LB (1998) Dietary reference intakes for folate: the debut of dietary folate equivalents. Nutr Rev 56:294–299

    Article  CAS  PubMed  Google Scholar 

  21. Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  23. Baggott JE, Morgan SL, Ha T, Vaughn WH, Hine RJ (1992) Inhibition of folate-dependent enzymes by non-steroidal anti-inflammatory drugs. Biochem J 282(Pt 1):197–202

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Linnebank M, Moskau S, Semmler A et al (2011) Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol 69:352–359

    Article  CAS  PubMed  Google Scholar 

  25. O’Leary F, Samman S (2010) Vitamin B12 in health and disease. Nutrients 2:299–316

    Article  PubMed Central  PubMed  Google Scholar 

  26. Bunin GR, Tseng M, Li Y, Meadows AT, Ganguly A (2012) Parental diet and risk of retinoblastoma resulting from new germline RB1 mutation. Environ Mol Mutagen 53:451–461

    Article  CAS  PubMed  Google Scholar 

  27. Bassett JK, Baglietto L, Hodge AM et al (2013) Dietary intake of B vitamins and methionine and breast cancer risk. Cancer Causes Control 24:1555–1563

    Article  PubMed  Google Scholar 

  28. Gong Z, Holly EA, Bracci PM (2009) Intake of folate, vitamins B6, B12 and methionine and risk of pancreatic cancer in a large population-based case–control study. Cancer Causes Control 20:1317–1325

    Article  PubMed Central  PubMed  Google Scholar 

  29. Weinstein SJ, Stolzenberg-Solomon R, Pietinen P, Taylor PR, Virtamo J, Albanes D (2006) Dietary factors of one-carbon metabolism and prostate cancer risk. Am J Clin Nutr 84:929–935

    CAS  PubMed  Google Scholar 

  30. Mayne ST, Risch HA, Dubrow R et al (2001) Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 10:1055–1062

    CAS  PubMed  Google Scholar 

  31. Kune G, Watson L (2006) Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer 56:11–21

    Article  CAS  PubMed  Google Scholar 

  32. Wu JW, Cross AJ, Baris D et al (2012) Dietary intake of meat, fruits, vegetables, and selective micronutrients and risk of bladder cancer in the New England region of the United States. Br J Cancer 106:1891–1898

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Friel S, Kelleher CC, Nolan G, Harrington J (2003) Social diversity of Irish adults nutritional intake. Eur J Clin Nutr 57:865–875

    Article  CAS  PubMed  Google Scholar 

  34. Hulshof KF, Brussaard JH, Kruizinga AG, Telman J, Lowik MR (2003) Socio-economic status, dietary intake and 10 y trends: the Dutch National Food Consumption Survey. Eur J Clin Nutr 57:128–137

    Article  CAS  PubMed  Google Scholar 

  35. Aston LM, Smith JN, Powles JW (2013) Meat intake in Britain in relation to other dietary components and to demographic and risk factor variables: analyses based on the National Diet and Nutrition Survey of 2000/2001. J Hum Nutr Diet 26:96–106

    Article  CAS  PubMed  Google Scholar 

  36. Bailey HD, Milne E, de Klerk NH et al (2011) Exposure to house painting and the use of floor treatments and the risk of childhood acute lymphoblastic leukemia. Int J Cancer 128:2405–2414

    Article  CAS  PubMed  Google Scholar 

  37. Johansson I, Van GB, Hultdin J, Johansson M, Hallmans G, Stattin P (2010) Validity of food frequency questionnaire estimated intakes of folate and other B vitamins in a region without folic acid fortification. Eur J Clin Nutr 64:905–913

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The Aus-ALL consortium conducted the study and the Telethon Kids Institute (Formally Telethon Institute for Child Health Research; TICHR), University of Western Australia, was the coordinating center. Bruce K. Armstrong (Sydney School of Public Health), Elizabeth Milne (TICHR), Frank M. van Bockxmeer (Royal Perth Hospital), Michelle Haber (Children’s Cancer Institute Australia), Rodney J. Scott (University of Newcastle), John Attia (University of Newcastle), Murray D. Norris (Children’s Cancer Institute Australia), Carol Bower (TICHR), Nicholas H. de Klerk (TICHR), Lin Fritschi (WA Institute for Medical Research), Ursula R. Kees (TICHR), Margaret Miller (Edith Cowan University), Judith R Thompson (WA Cancer Registry) were the research investigators, and Helen D. Bailey (TICHR) was the project coordinator. The clinical investigators were Frank Alvaro (John Hunter Hospital, Newcastle), Catherine Cole (Princess Margaret Hospital for Children, Perth), Luciano Dalla Pozza (Children’s Hospital at Westmead, Sydney), John Daubenton (Royal Hobart Hospital, Hobart), Peter Downie (Monash Medical Centre, Melbourne), Liane Lockwood (Royal Children’s Hospital, Brisbane), Maria Kirby (Women’s and Children’s Hospital, Adelaide), Glenn Marshall (Sydney Children’s Hospital, Sydney), Elizabeth Smibert (Royal Children’s Hospital, Melbourne), and Ram Suppiah (previously Mater Children’s Hospital, Brisbane). The authors wish to acknowledge the contribution made by our Clinical Co-Investigators and Clinical Research Associates who recruited and cared for study patients at each participating hospital, and Mr Peter Cosgrove for programming the estimation of dietary intake from the food frequency questionnaires. The authors also thank the parents and children who participated in Aus-ALL.

Conflict of interest

The authors declare no conflict of interest. Aus-ALL was funded by The National Health and Medical Research Council (NHMRC) Grant 254539. Helen Bailey was supported by NHMRC Postgraduate Scholarship 513934, Elizabeth Milne by NHMRC Career Development Award 513910, and Carol Bower by NHMRC Research Fellowship 634341.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Helen D. Bailey.

Additional information

For the Aus-ALL Consortium.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 32 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bailey, H.D., Miller, M., Greenop, K.R. et al. Paternal intake of folate and vitamins B6 and B12 before conception and risk of childhood acute lymphoblastic leukemia. Cancer Causes Control 25, 1615–1625 (2014). https://doi.org/10.1007/s10552-014-0466-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-014-0466-3

Keywords

Navigation