Advertisement

Cancer Causes & Control

, Volume 26, Issue 11, pp 1575–1582 | Cite as

Birth order and risk of childhood cancer in the Danish birth cohort of 1973–2010

  • Joachim SchüzEmail author
  • George Luta
  • Friederike Erdmann
  • Gilles Ferro
  • Andrea Bautz
  • Sofie Bay Simony
  • Susanne Oksbjerg Dalton
  • Tracy Lightfoot
  • Jeanette Falck Winther
Original paper

Abstract

Purpose

Many studies have investigated the possible association between birth order and risk of childhood cancer, although the evidence to date has been inconsistent. Birth order has been used as a marker for various in utero or childhood exposures and is relatively straightforward to assess.

Methods

Data were obtained on all children born in Denmark between 1973 and 2010, involving almost 2.5 million births and about 5,700 newly diagnosed childhood cancers before the age of 20 years. Data were analyzed using Poisson regression models.

Results

We failed to observe associations between birth order and risk of any childhood cancer subtype, including acute lymphoblastic leukemia; all rate ratios were close to one. Further analyses stratified by birth cohort (those born between 1973 and 1990, and those born between 1991 and 2010) also failed to show any associations. Considering stillbirths and/or controlling for birth weight and parental age in the analyses had no effect on the results. Analyses by years of birth (those born between 1973 and 1990, and those born between 1991 and 2010) did not show any changes in the overall pattern of no association.

Conclusions

In this large cohort of all children born in Denmark over an almost 40-year period, we did not observe an association between birth order and the risk of childhood cancer.

Keywords

Birth order Childhood cancer Leukemia Risk factors Denmark 

Abbreviations

ALL

Acute lymphoblastic leukemia

AML

Acute myeloblastic leukemia

CNS

Central nervous system

RR

Rate ratio

CI

95 % Confidence interval

Notes

Acknowledgments

No specific funding was obtained for this study. Costs for data retrieval were covered by the collaboration agreement between the IARC and the Danish Cancer  Society Research Center.

Compliance with ethical standards

Conflict of interest

None of the authors declared any conflict of interest.

Human and animal rights

The study did not involve personal contact with human subjects and no animals. The study is based on record linkage of various registers in Denmark and was therefore approved by “Datatilsynet” (the Danish Data Protection Board). No informed consent from individuals was required.

References

  1. 1.
    Little J (1999) Epidemiology of childhood cancer. IARC Science Publication, Lyon, p 149Google Scholar
  2. 2.
    Savage S, Schüz J (2011) Environmental chemicals and childhood cancer. In: Nriagu J (ed) Encyclopedia of environmental health. Elsevier, Amsterdam, pp 336–347CrossRefGoogle Scholar
  3. 3.
    Buffler P, Kwan M, Reynolds P, Urayama K (2005) Environmental and genetic risk factors for childhood leukemia: appraising the evidence. Cancer Invest 23(1):60–75CrossRefPubMedGoogle Scholar
  4. 4.
    Von Behren J, Spector LG, Mueller BA, Carozza SE, Chow EJ, Fox EE, Horel S, Johnson KJ, McLaughlin C, Puumala SE, Ross JA, Reynolds P (2011) Birth order and risk of childhood cancer: a pooled analysis from five US States. Int J Cancer 128(11):2709–2716CrossRefGoogle Scholar
  5. 5.
    Hjalgrim LL, Rostgaard K, Hjalgrim H, Westergaard T, Thomassen H, Forestier E, Gustafsson G, Kristinsson J, Melbye M, Schmiegelow K (2004) Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway, and Iceland. J Natl Cancer Inst 96(20):1549–1556CrossRefPubMedGoogle Scholar
  6. 6.
    Oksuzyan S, Crespi CM, Cockburn M, Mezei G, Kheifets L (2012) Birth weight and other perinatal characteristics and childhood leukemia in California. Cancer Epidemiol 36(6):e359–e365PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Marcotte EL, Ritz B, Cockburn M, Yu F, Heck JE (2014) Exposure to infections and risk of leukemia in young children. Cancer Epidemiol Biomarker Prev 23(7):1195–1203Google Scholar
  8. 8.
    Rudant J, Lightfoot T, Urayama KY, Petridou E, Dockerty JD, Magnani C, Milne L, Spector LG, Ashton L, Dessypris N, Kang AY, Miller M, Rondelli R, Simpson J, Stiakaki E, Orsi L, Roman E, Metayer C, Infante-Rivard C, Clavel J (2015) Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a childhood leukemia international consortium (CLIC). Am J Epidemiol 181:549–562CrossRefPubMedGoogle Scholar
  9. 9.
    Schüz J, Kaatsch P, Kaletsch U, Meinert R, Michaelis J (1999) Association of childhood cancer with factors related to pregnancy and birth. Int J Epidemiol 28(4):631–639CrossRefPubMedGoogle Scholar
  10. 10.
    Schmidt LS, Kamper-Jørgensen M, Schmiegelow K, Johansen C, Lähteenmäki P, Träger C, Stokland T, Grell K, Gustafson G, Kogner P, Sehested A, Schüz J (2010) Infectious exposure in the first years of life and risk of central nervous system tumours in children: analysis of birth order, childcare attendance and seasonality of birth. Br J Cancer 102(11):1670–1675PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Schüz J, Schmidt LS, Kogner P, Lähteenmäki PM, Pal N, Stokland T, Schmiegelow K (2011) Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case–control study. Int J Cancer 128(9):2166–2173CrossRefPubMedGoogle Scholar
  12. 12.
    Johnson KJ, Carozza SE, Chow EJ, Fox EE, Horel S, McLaughlin CC, Mueller BA, Puumala SE, Reynolds P, Von Behren J, Spector LG (2011) Birth characteristics and childhood carcinomas. Br J Cancer 105(9):1396–1401PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Olson JE, Shu XO, Ross JA, Pendergrass T, Robison LL (1997) Medical record validation of maternally reported birth characteristics and pregnancy-related events: a report from the Children’s Cancer Group. Am J Epidemiol 145(1):58–67CrossRefPubMedGoogle Scholar
  14. 14.
    Crouch S, Lightfoot T, Simpson J, Smith A, Ansell P, Roman E (2012) Infectious illness in children subsequently diagnosed with acute lymphoblastic leukemia: modeling the trends from birth to diagnosis. Am J Epidemiol 176(5):402–408CrossRefPubMedGoogle Scholar
  15. 15.
    Wiemels J (2012) Perspectives on the causes of childhood leukemia. Chem Biol Interact 196(3):59–67CrossRefPubMedGoogle Scholar
  16. 16.
    Greaves MF (2001) Commentary: birth order and risk of childhood acute lymphoblastic leukaemia (ALL). Int J Epidemiol 30(6):1438–1439CrossRefPubMedGoogle Scholar
  17. 17.
    Greaves M (1999) Molecular genetics, natural history and the demise of childhood leukaemia. Eur J Cancer 35(2):173–185CrossRefPubMedGoogle Scholar
  18. 18.
    Greaves M (2006) Infection, immune responses and the aetiology of childhood leukaemia. Nat Rev Cancer 6(3):193–203CrossRefPubMedGoogle Scholar
  19. 19.
    Roman E, Simpson J, Ansell P, Lightfoot T, Smith A (2009) Infectious proxies and childhood leukaemia: findings from the United Kingdom Childhood Cancer Study (UKCCS). Blood Cells Mol Dis 42(2):126–128CrossRefPubMedGoogle Scholar
  20. 20.
    Roman E, Simpson J, Ansell P, Kinsey S, Mitchell CD, McKinney PA, Birch JM, Greaves M (2007) Eden T; United Kingdom Childhood Cancer Study Investigators. Childhood acute lymphoblastic leukemia and infections in the first year of life: a report from the United Kingdom Childhood Cancer Study. Am J Epidemiol 165(5):496–504CrossRefPubMedGoogle Scholar
  21. 21.
    Simpson J, Smith A, Ansell P, Roman E (2007) Childhood leukaemia and infectious exposure: a report from the United Kingdom Childhood Cancer Study (UKCCS). Eur J Cancer 43(16):2396–2403CrossRefPubMedGoogle Scholar
  22. 22.
    Bernstein L, Depue RH, Ross RK, Judd HL, Pike MC, Henderson BE (1986) Higher maternal levels of free estradiol in first compared to second pregnancy: early gestational differences. J Natl Cancer Inst 76(6):1035–1039PubMedGoogle Scholar
  23. 23.
    Maccoby EE, Doering CH, Jacklin CN, Kraemer H (1979) Concentrations of sex hormones in umbilical-cord blood: their relation to sex and birth order of infants. Child Dev 50(3):632–642CrossRefPubMedGoogle Scholar
  24. 24.
    Cook MB, Akre O, Forman D, Madigan MP, Richiardi L, McGlynn KA (2009) A systematic review and meta-analysis of perinatal variables in relation to the risk of testicular cancer–experiences of the mother. Int J Epidemiol 38(6):1532–1542PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Juntunen KS, Läärä EM, Kauppila AJ (1997) Grand grand multiparity and birth weight. Obstet Gynecol 90:495–499CrossRefPubMedGoogle Scholar
  26. 26.
    Harder T, Plagemann A, Harder A (2008) Birth weight and subsequent risk of childhood primary brain tumors: a meta-analysis. Am J Epidemiol 168(4):366–373CrossRefPubMedGoogle Scholar
  27. 27.
    Harder T, Plagemann A, Harder A (2010) Birth weight and risk of neuroblastoma: a meta-analysis. Int J Epidemiol 39(3):746–756CrossRefPubMedGoogle Scholar
  28. 28.
    Jones M, Jeal H, Harris JM, Smith JD, Rose ML, Taylor AN, Cullinan P (2013) Association of maternal anti-HLA class II antibodies with protection from allergy in offspring. Allergy 68(9):1143–1149PubMedGoogle Scholar
  29. 29.
    Schüz J, Forman MR (2007) Birthweight by gestational age and childhood cancer. Cancer Causes Control 18(6):655–663CrossRefPubMedGoogle Scholar
  30. 30.
    Schüz J (2003) Non-response bias as a likely cause of the association between young maternal age at the time of delivery and the risk of cancer in the offspring. Paediatr Perinat Epidemiol 17(1):106–112CrossRefPubMedGoogle Scholar
  31. 31.
    Thygesen LC, Daasnes C, Thaulow I, Bronnum-Hansen H (2011) Introduction to Danish (nationwide) registers on health and social issues: structure, access, legislation, and archiving. Scand J Public Health 39(7 Suppl):12–16CrossRefPubMedGoogle Scholar
  32. 32.
    Gjerstorff ML (2011) The Danish Cancer Registry. Scand J Public Health 39(7 Suppl):42–45CrossRefPubMedGoogle Scholar
  33. 33.
    Nguyen-Nielsen M, Svensson E, Vogel I, Ehrenstein V, Sunde L (2013) Existing data sources for clinical epidemiology: Danish registries for studies of medical genetic diseases. Clin Epidemiol. 5:249–262PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Birch JM, Marsden HB (1987) A classification scheme for childhood cancer. Int J Cancer 40(5):620–624CrossRefPubMedGoogle Scholar
  35. 35.
    Steliarova-Foucher E, Stiller C, Lacour B, Kaatsch P (2005) International classification of childhood cancer, third edition. Cancer 103(7):1457–1467CrossRefPubMedGoogle Scholar
  36. 36.
    SAS/STAT software, Version 9.3 of the SAS System for Windows. Copyright © 2002–2010 SAS Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered trademarks or trademarks of SAS Institute Inc., Cary, NC, USAGoogle Scholar
  37. 37.
    Raaschou-Nielsen O, Obel J, Dalton S, Tjønneland A, Hansen J (2004) Socioeconomic status and risk of childhood leukaemia in Denmark. Scand J Public Health. 32(4):279–286CrossRefPubMedGoogle Scholar
  38. 38.
    Westergaard T, Andersen PK, Pedersen JB, Olsen JH, Frisch M, Sørensen HT, Wohlfahrt J, Melbye M (1997) Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study. J Natl Cancer Inst 89:939–947CrossRefPubMedGoogle Scholar
  39. 39.
    Crump C, Sundquist J, Sieh W, Winkleby MA, Sundquist K (2015) Perinatal and familial risk factors for acute lymphoblastic leukemia in a Swedish national cohort. Cancer 121:1040–1047CrossRefPubMedGoogle Scholar
  40. 40.
    Petersen AN (editor). Børns levevilkår [Childrens living conditions]. Statistics Denmark 2002; Statistics Denmark Printing, Copenhagen; ISBN 87-501-1286-4Google Scholar
  41. 41.
    Jones M, Jeal H, Harris JM, Smith JD, Rose ML, Taylor AN, Cullinan P (2013) Association of maternal anti-HLA class II antibodies with protection from allergy in offspring. Allergy 68:1143–1149PubMedGoogle Scholar
  42. 42.
    Karmaus W, Arshad SH, Sadeghnejad A, Twiselton R (2004) Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance. Clin Exp Allergy 34:853–859CrossRefPubMedGoogle Scholar
  43. 43.
    Puumala SE, Ross JA, Aplenc R, Spector LG (2013) Epidemiology of childhood acute myeloid leukemia. Pediatr Blood Cancer 60(5):728–733PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Westergaard T, Melbye M, Pedersen JB, Frisch M, Olsen JH, Andersen PK (1997) Birth order, sibship size and risk of Hodgkin’s disease in children and young adults: a population-based study of 31 million person-years. Int J Cancer 72:977–981CrossRefPubMedGoogle Scholar
  45. 45.
    Heck JE, Ritz B, Hung RJ, Hashibe M, Boffetta P (2009) The epidemiology of neuroblastoma: a review. Paediatr Perinat Epidemiol 23(2):125–143CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Joachim Schüz
    • 1
    Email author
  • George Luta
    • 2
  • Friederike Erdmann
    • 1
  • Gilles Ferro
    • 1
  • Andrea Bautz
    • 3
  • Sofie Bay Simony
    • 4
  • Susanne Oksbjerg Dalton
    • 4
  • Tracy Lightfoot
    • 1
    • 5
  • Jeanette Falck Winther
    • 3
  1. 1.Section of Environment and RadiationInternational Agency for Research on Cancer (IARC)LyonFrance
  2. 2.Department of Biostatistics, Bioinformatics and BiomathematicsGeorgetown UniversityWashingtonUSA
  3. 3.Survivorship Unit, Childhood Cancer Survivorship Research GroupDanish Cancer Society Research CenterCopenhagenDenmark
  4. 4.Survivorship Unit, Social Inequality in Survivorship GroupDanish Cancer Society Research CenterCopenhagenDenmark
  5. 5.Epidemiology and Cancer Statistics Group, Department of Health SciencesUniversity of YorkYorkUK

Personalised recommendations