EPIDEMIOLOGY OF INFANT LEUKEMIA

Summary

Principal Investigator: JULIE ANN ROSS
Affiliation: University of Minnesota
Country: USA
Abstract: DESCRIPTION (provided by applicant): The study of rare cancers has led to major findings in cancer etiology. Infants with leukemia may represent another such rare group. Infants with leukemia are clinically, epidemiologically, and biologically distinct from older children with leukemia. Approximately 60% of infants with acute myeloid leukemia (AML) and 75% of infants with acute lymphoblastic leukemia (ALL) present with an MLL gene rearrangement in their leukemia cells. Molecular studies demonstrate that infant leukemia's arise in utero. Our preliminary data indicate that maternal exposure to environmental agents, including DNA topoisomerase II inhibitors, are important in the etiology of infant leukemia. Further, others and we have evidence to suggest that the etiology of MLL positive infant leukemia is distinctly different from MLL negative infant leukemia. We are uniquely positioned to expand our current study to increase the statistical power to evaluate associations between MLL positive and MLL negative infant leukemia. Further, we can collect DNA retrospectively and prospectively from both mothers and infants to investigate the role of specific genetic polymorphisms in the etiology of infant leukemia. Our specific aims are to: a) interview an additional 240 mothers of infant cases (bringing the case total to 484) to increase the statistical power and make this the largest study to ask whether specific chemicals are associated with MLL infant leukemia; b) obtain DNA from infant cases to investigate genetic polymorphisms (including NQ01, MTHFR, GSTM1, GSTT1, GSTPi, MPO, COMT, IGF1) associated with infant leukemia; c) obtain DNA from case mothers and investigate the genetic polymorphisms described above in association with infant leukemia; and d) explore gene-environment interactions in the etiology of MLL infant leukemia. We hypothesize that specific exposure, including those associated with DNA Topoisomerase II inhibition, are more often associated with MLL-positive infant leukemia. Further, we hypothesize that genetic differences in the ability to detoxify environmental toxins contributes to genetic susceptibility to MLL-positive leukemia. Finally, we hypothesize that unfavorable genotypes, in combination with exposure to specific agents, increases the risk of MLL infant leukemia. This study will utilize the unique resources available through the Children's Oncology Group, and include ascertainment of cases over a four-year period (Jan 1, 2003-Dec 31, 2006).
Funding Period: 1999-02-09 - 2009-03-31
more information: NIH RePORT

Top Publications

  1. pmc Excess congenital non-synonymous variation in leukemia-associated genes in MLL- infant leukemia: a Children's Oncology Group report
    M C Valentine
    1 Department of Genetics, Washington University School of Medicine, St Louis, MO, USA 2 Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA
    Leukemia 28:1235-41. 2014
  2. pmc Genetic variants modify susceptibility to leukemia in infants: a Children's Oncology Group report
    Julie A Ross
    Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
    Pediatr Blood Cancer 60:31-4. 2013
  3. pmc Maternal prenatal cigarette, alcohol and illicit drug use and risk of infant leukaemia: a report from the Children's Oncology Group
    Megan E Slater
    Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, 55455, USA
    Paediatr Perinat Epidemiol 25:559-65. 2011
  4. pmc Self-report versus medical record - perinatal factors in a study of infant leukaemia: a study from the Children's Oncology Group
    Anne M Jurek
    Exponent Inc Health Sciences, Washington, DC, USA
    Paediatr Perinat Epidemiol 25:540-8. 2011
  5. pmc MLL gene rearrangements in infant leukemia vary with age at diagnosis and selected demographic factors: a Children's Oncology Group (COG) study
    Thien N Sam
    University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota
    Pediatr Blood Cancer 58:836-9. 2012
  6. pmc Maternal exposure to household chemicals and risk of infant leukemia: a report from the Children's Oncology Group
    Megan E Slater
    Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
    Cancer Causes Control 22:1197-204. 2011
  7. pmc Analgesic use during pregnancy and risk of infant leukaemia: a Children's Oncology Group study
    S Ognjanovic
    Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, 420 Delaware Street SE, MMC 422, Minneapolis, MN 55455, USA
    Br J Cancer 104:532-6. 2011
  8. pmc Maternal vitamin and iron supplementation and risk of infant leukaemia: a report from the Children's Oncology Group
    A M Linabery
    Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, 420 Delaware Street SE, MMC 422, Minneapolis, MN 55455, USA
    Br J Cancer 103:1724-8. 2010
  9. pmc Infant leukemia and congenital abnormalities: a Children's Oncology Group study
    Kimberly J Johnson
    Division of Epidemiology Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
    Pediatr Blood Cancer 55:95-9. 2010
  10. pmc Infant leukemia and parental infertility or its treatment: a Children's Oncology Group report
    Susan E Puumala
    Division of Epidemiology Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
    Hum Reprod 25:1561-8. 2010

Scientific Experts

  • L Spector
  • J A Ross
  • Greta R Bunin
  • Simona Ognjanovic
  • Anne M Jurek
  • Amy M Linabery
  • Nyla A Heerema
  • Megan E Slater
  • Kimberly J Johnson
  • Leslie L Robison
  • Susan E Puumala
  • A M Linabery
  • Joanne M Hilden
  • Michelle A Roesler
  • M C Valentine
  • N A Heerema
  • J M Hilden
  • Thien N Sam
  • Stella M Davies
  • Cindy K Blair
  • A M Peters
  • N Sanchez
  • A E O Hughes
  • C Mallaney
  • S Chasnoff
  • J Giacalone
  • T E Druley
  • John H Kersey
  • Gregory H Reaman
  • S E Puumala
  • M A Roesler
  • Melanie M Wall
  • S M Davies
  • Andrew F Olshan
  • G H Reaman
  • J P Neglia
  • M R Verneris
  • C K Blair
  • C A Felix
  • L L Robison

Detail Information

Publications18

  1. pmc Excess congenital non-synonymous variation in leukemia-associated genes in MLL- infant leukemia: a Children's Oncology Group report
    M C Valentine
    1 Department of Genetics, Washington University School of Medicine, St Louis, MO, USA 2 Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA
    Leukemia 28:1235-41. 2014
    ..This model would be consistent with existing models for the establishment of leukemia clones in utero and the high rate of IL concordance in monozygotic twins. ..
  2. pmc Genetic variants modify susceptibility to leukemia in infants: a Children's Oncology Group report
    Julie A Ross
    Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
    Pediatr Blood Cancer 60:31-4. 2013
    ..Genetic determinants of susceptibility to IL are unknown. Recent genome-wide association studies for childhood acute lymphoblastic leukemia (ALL) have identified susceptibility loci at IKZF1, ARID5B, and CEBPE...
  3. pmc Maternal prenatal cigarette, alcohol and illicit drug use and risk of infant leukaemia: a report from the Children's Oncology Group
    Megan E Slater
    Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, 55455, USA
    Paediatr Perinat Epidemiol 25:559-65. 2011
    ..Future case-control studies of childhood leukaemia that pursue these exposures may benefit from incorporation of validated instruments and/or biomarkers when feasible...
  4. pmc Self-report versus medical record - perinatal factors in a study of infant leukaemia: a study from the Children's Oncology Group
    Anne M Jurek
    Exponent Inc Health Sciences, Washington, DC, USA
    Paediatr Perinat Epidemiol 25:540-8. 2011
    ..7 years for control mothers. Many conditions exhibited notable differences between interview and records. We recommend use of multiple measurement sources to allow both cross-checking and synthesis of results into more accurate measures...
  5. pmc MLL gene rearrangements in infant leukemia vary with age at diagnosis and selected demographic factors: a Children's Oncology Group (COG) study
    Thien N Sam
    University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota
    Pediatr Blood Cancer 58:836-9. 2012
    ..Infant leukemias have a high frequency of mixed lineage leukemia (MLL) gene rearrangements...
  6. pmc Maternal exposure to household chemicals and risk of infant leukemia: a report from the Children's Oncology Group
    Megan E Slater
    Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
    Cancer Causes Control 22:1197-204. 2011
    ..Utilizing data from the largest study to date, we examined associations between maternal preconception/prenatal exposure to household chemicals and infant acute leukemia...
  7. pmc Analgesic use during pregnancy and risk of infant leukaemia: a Children's Oncology Group study
    S Ognjanovic
    Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, 420 Delaware Street SE, MMC 422, Minneapolis, MN 55455, USA
    Br J Cancer 104:532-6. 2011
    ..Infant leukaemia is likely initiated in utero...
  8. pmc Maternal vitamin and iron supplementation and risk of infant leukaemia: a report from the Children's Oncology Group
    A M Linabery
    Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, 420 Delaware Street SE, MMC 422, Minneapolis, MN 55455, USA
    Br J Cancer 103:1724-8. 2010
    ..Prenatal supplementation has been inversely associated with childhood, but not with infant, leukaemia...
  9. pmc Infant leukemia and congenital abnormalities: a Children's Oncology Group study
    Kimberly J Johnson
    Division of Epidemiology Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
    Pediatr Blood Cancer 55:95-9. 2010
    ..Differences in survival and the molecular characteristics of leukemia in infants versus older children suggest a distinct etiology, likely involving prenatal factors...
  10. pmc Infant leukemia and parental infertility or its treatment: a Children's Oncology Group report
    Susan E Puumala
    Division of Epidemiology Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
    Hum Reprod 25:1561-8. 2010
    ..Parental infertility and infertility treatment have been studied with regard to childhood cancer in general, but rarely in individual cancer subtypes...
  11. pmc Comparability and representativeness of control groups in a case-control study of infant leukemia: a report from the Children's Oncology Group
    Susan E Puumala
    Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
    Am J Epidemiol 170:379-87. 2009
    ..3,317 g). Finally, participating BC mothers were likely to be older and to have more education than nonparticipants. Thus, the study's control groups were comparable but differed from the population of interest...
  12. ncbi Feasibility of nationwide birth registry control selection in the United States
    Logan G Spector
    Division of Epidemiology Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
    Am J Epidemiol 166:852-6. 2007
    ..These results suggest that birth registries may be used to select controls for studies of rare childhood diseases on a national scale...
  13. ncbi Secular trends in response rates for controls selected by random digit dialing in childhood cancer studies: a report from the Children's Oncology Group
    Greta R Bunin
    Division of Oncology, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Am J Epidemiol 166:109-16. 2007
    ..4% per year (95% CI: -2.7, -2.0; p < 0.001). The current low response rates for RDD indicate a substantial potential for selection bias and a need to seek alternative sources of controls...
  14. ncbi Birth characteristics, maternal reproductive history, and the risk of infant leukemia: a report from the Children's Oncology Group
    Logan G Spector
    Division of Epidemiology Clinical Research, Department of Pediatrics, University of Minnesota, 420 Delaware Street Southeast, MMC 715, Minneapolis, MN 55455, USA
    Cancer Epidemiol Biomarkers Prev 16:128-34. 2007
    ..Other variables of interest were not notably associated with infant leukemia regardless of MLL status. This investigation further supports the contention that molecularly defined subtypes of infant leukemia have separate etiologies...
  15. pmc Maternal hemoglobin concentration during pregnancy and risk of infant leukaemia: a children's oncology group study
    A M Peters
    Department of Pediatrics, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, USA
    Br J Cancer 95:1274-6. 2006
    ..In contrast to the positive association found in three studies between maternal anaemia during pregnancy and childhood leukaemia, no such association was found in infant leukaemia (odds ratio 0.85, 95% confidence interval 0.53-1.37)...
  16. ncbi Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group
    Logan G Spector
    Division of Pediatric Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
    Cancer Epidemiol Biomarkers Prev 14:651-5. 2005
    ..We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+)...