Cancer Causes & Control

, Volume 22, Issue 8, pp 1197–1204

Maternal exposure to household chemicals and risk of infant leukemia: a report from the Children’s Oncology Group

  • Megan E. Slater
  • Amy M. Linabery
  • Logan G. Spector
  • Kimberly J. Johnson
  • Joanne M. Hilden
  • Nyla A. Heerema
  • Leslie L. Robison
  • Julie A. Ross
Original paper



Utilizing data from the largest study to date, we examined associations between maternal preconception/prenatal exposure to household chemicals and infant acute leukemia.


We present data from a Children’s Oncology Group case–control study of 443 infants (<1 year of age) diagnosed with acute leukemia [including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)] between 1996 and 2006 and 324 population controls. Mothers recalled household chemical use 1 month before and throughout pregnancy. We used unconditional logistic regression adjusted for birth year, maternal age, and race/ethnicity to calculate odds ratios (ORs) and 95% confidence intervals (CIs).


We did not find evidence for an association between infant leukemia and eight of nine chemical categories. However, exposure to petroleum products during pregnancy was associated with AML (OR = 2.54; 95% CI:1.40–4.62) and leukemia without mixed lineage leukemia (MLL) gene rearrangements (“MLL−”) (OR = 2.69; 95% CI: 1.47–4.93). No associations were observed for exposure in the month before pregnancy.


Gestational exposure to petroleum products was associated with infant leukemia, particularly AML, and MLL− cases. Benzene is implicated as a potential carcinogen within this exposure category, but a clear biological mechanism has yet to be elucidated.


Epidemiology Infants Leukemia Chemical Prenatal 


  1. 1.
    Linabery AM, Ross JA (2008) Trends in childhood cancer incidence in the US (1992–2004). Cancer 112:416–432PubMedCrossRefGoogle Scholar
  2. 2.
    Linabery AM, Ross JA (2008) Childhood and adolescent cancer survival in the US by race and ethnicity for the diagnostic period 1975–1999. Cancer 113:2575–2596PubMedCrossRefGoogle Scholar
  3. 3.
    Ross JA (2000) Dietary flavonoids and the MLL gene: a pathway to infant leukemia? Proc Natl Acad Sci USA 97:4411–4413PubMedCrossRefGoogle Scholar
  4. 4.
    Krivtsov AV, Armstrong SA (2007) MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 7:823–833PubMedCrossRefGoogle Scholar
  5. 5.
    Eden T (2010) Aetiology of childhood leukaemia. Cancer Treat Rev 36:286–297PubMedCrossRefGoogle Scholar
  6. 6.
    Stam RW, Schneider P, Hagelstein JA, van der Linden MH, Stumpel DJ et al (2010) Gene expression profiling-based dissection of MLL translocated and MLL germline acute lymphoblastic leukemia in infants. Blood 115:2835–2844PubMedCrossRefGoogle Scholar
  7. 7.
    Chowdhury T, Brady HJ (2008) Insights from clinical studies into the role of the MLL gene in infant and childhood leukemia. Blood Cells Mol Dis 40:192–199PubMedCrossRefGoogle Scholar
  8. 8.
    Greaves MF, Maia AT, Wiemels JL, Ford AM (2003) Leukemia in twins: lessons in natural history. Blood 102:2321–2333PubMedCrossRefGoogle Scholar
  9. 9.
    Gale KB, Ford AM, Repp R, Borkhardt A, Keller C et al (1997) Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA 94:13950–13954PubMedCrossRefGoogle Scholar
  10. 10.
    Smith MT (2010) Advances in understanding benzene health effects and susceptibility. Annu Rev Public Health 31:133–148 132 p following 148PubMedCrossRefGoogle Scholar
  11. 11.
    Buffler PA, Kwan ML, Reynolds P, Urayama KY (2005) Environmental and genetic risk factors for childhood leukemia: appraising the evidence. Cancer Invest 23:60–75PubMedGoogle Scholar
  12. 12.
    Turner MC, Wigle DT, Krewski D (2010) Residential pesticides and childhood leukemia: a systematic review and meta-analysis. Environ Health Perspect 118:33–41PubMedCrossRefGoogle Scholar
  13. 13.
    Pombo-de-Oliveira MS, Koifman S (2006) Infant acute leukemia and maternal exposures during pregnancy. Cancer Epidemiol Biomarkers Prev 15:2336–2341PubMedCrossRefGoogle Scholar
  14. 14.
    Alexander FE, Patheal SL, Biondi A, Brandalise S, Cabrera ME et al (2001) Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion. Cancer Res 61:2542–2546PubMedGoogle Scholar
  15. 15.
    Puumala SE, Spector LG, Robison LL, Bunin GR, Olshan AF et al (2009) Comparability and representativeness of control groups in a case-control study of infant leukemia: a report from the children’s oncology group. Am J Epidemiol 170:379–387PubMedCrossRefGoogle Scholar
  16. 16.
    Johnson KJ, Roesler MA, Linabery AM, Hilden JM, Davies SM et al (2010) Infant leukemia and congenital abnormalities: a children’s oncology group study. Pediatr Blood Cancer 55:95–99PubMedGoogle Scholar
  17. 17.
    Puumala SE, Spector LG, Wall MM, Robison LL, Heerema NA et al (2010) Infant leukemia and parental infertility or its treatment: a children’s oncology group report. Hum Reprod 25:1561–1568PubMedCrossRefGoogle Scholar
  18. 18.
    Robison LL, Daigle A (1984) Control selection using random digit dialing for cases of childhood cancer. Am J Epidemiol 120:164–166PubMedGoogle Scholar
  19. 19.
    Waksberg JS (1978) Sampling methods for random digit dialing. J Am Stat Assoc 73:40–46CrossRefGoogle Scholar
  20. 20.
    Spector LG, Xie Y, Robison LL, Heerema NA, Hilden JM 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 14:651–655PubMedCrossRefGoogle Scholar
  21. 21.
    Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML et al (2002) MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 30:41–47PubMedCrossRefGoogle Scholar
  22. 22.
    Rothman KJ, Greenland S, Lash TL (2008) Modern epidemiology. Lippincott Williams & Wilkins, Philadelphia p. 345–380Google Scholar
  23. 23.
    Mondrala S, Eastmond DA (2010) Topoisomerase II inhibition by the bioactivated benzene metabolite hydroquinone involves multiple mechanisms. Chem Biol Interact 184:259–268PubMedCrossRefGoogle Scholar
  24. 24.
    Schnatter AR, Rosamilia K, Wojcik NC (2005) Review of the literature on benzene exposure and leukemia subtypes. Chem Biol Interact 153–154:9–21PubMedCrossRefGoogle Scholar
  25. 25.
    Pyatt D, Hays S (2010) A review of the potential association between childhood leukemia and benzene. Chem Biol Interact 184:151–164PubMedCrossRefGoogle Scholar
  26. 26.
    Scelo G, Metayer C, Zhang L, Wiemels JL, Aldrich MC et al (2009) Household exposure to paint and petroleum solvents, chromosomal translocations, and the risk of childhood leukemia. Environ Health Perspect 117:133–139PubMedGoogle Scholar
  27. 27.
    Dowty BJ, Laseter JL, Storer J (1976) The transplacental migration and accumulation in blood of volatile organic constituents. Pediatr Res 10:696–701PubMedGoogle Scholar
  28. 28.
    Ross ME, Mahfouz R, Onciu M, Liu HC, Zhou X et al (2004) Gene expression profiling of pediatric acute myelogenous leukemia. Blood 104:3679–3687PubMedCrossRefGoogle Scholar
  29. 29.
    Corti M, Snyder CA (1998) Gender- and age-specific cytotoxic susceptibility to benzene metabolites in vitro. Toxicol Sci 41:42–48PubMedGoogle Scholar
  30. 30.
    Keller KA, Snyder CA (1986) Mice exposed in utero to low concentrations of benzene exhibit enduring changes in their colony forming hematopoietic cells. Toxicology 42:171–181PubMedCrossRefGoogle Scholar
  31. 31.
    Infante-Rivard C, Weichenthal S (2007) Pesticides and childhood cancer: an update of Zahm and Ward’s 1998 review. J Toxicol Environ Health B Crit Rev 10:81–99PubMedGoogle Scholar
  32. 32.
    Metayer C, Buffler PA (2008) Residential exposures to pesticides and childhood leukaemia. Radiat Prot Dosimetry 132:212–219PubMedCrossRefGoogle Scholar
  33. 33.
    Lichter SR, Rothman S (1999) Environmental cancer–a political disease?, vol xiii. Yale University Press, New Haven, pp 235Google Scholar
  34. 34.
    Harris SA (2007) Assessment of pesticide exposure for epidemiological research: measurement error and bias. In: Krieger RI, Ragsdale NN, Seiber JN (eds) Assessing exposures and reducing risks to people from the use of pesticides. American Chemical Society; Distributed by Oxford University Press, Washington, pp 173–186CrossRefGoogle Scholar
  35. 35.
    Ross JA, Severson RK, Pollock BH, Robison LL (1996) Childhood cancer in the United States. A geographical analysis of cases from the pediatric cooperative clinical trials groups. Cancer 77:201–207PubMedCrossRefGoogle Scholar
  36. 36.
    Liu L, Krailo M, Reaman GH, Bernstein L (2003) Childhood cancer patients’ access to cooperative group cancer programs: a population-based study. Cancer 97:1339–1345PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Megan E. Slater
    • 1
  • Amy M. Linabery
    • 1
  • Logan G. Spector
    • 1
  • Kimberly J. Johnson
    • 1
  • Joanne M. Hilden
    • 2
  • Nyla A. Heerema
    • 3
  • Leslie L. Robison
    • 4
  • Julie A. Ross
    • 1
    • 5
    • 6
  1. 1.Division of Pediatric Epidemiology and Clinical Research, Department of PediatricsUniversity of MinnesotaMinneapolisUSA
  2. 2.Peyton Manning Children’s Hospital at St. VincentIndianapolisUSA
  3. 3.Department of PathologyThe Ohio State UniversityColumbusUSA
  4. 4.Department of Epidemiology and Cancer ControlSt. Jude Children’s Research HospitalMemphisUSA
  5. 5.University of Minnesota Cancer CenterMinneapolisUSA
  6. 6.Department of PediatricsUniversity of MinnesotaMinneapolisUSA

Personalised recommendations