EPIDEMIOLOGY OF INFANT LEUKEMIA

Summary

Principal Investigator: JULIE ANN ROSS
Affiliation: University of Minnesota
Country: USA
Abstract: 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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

Scientific Experts

  • L Spector
  • Greta R Bunin
  • Susan E Puumala
  • A M Peters
  • Julie A Ross
  • Leslie L Robison
  • Andrew F Olshan
  • Cindy K Blair
  • Amy M Linabery
  • Michelle A Roesler
  • C K Blair
  • J P Neglia
  • M R Verneris
  • L L Robison
  • G H Reaman
  • J A Ross
  • C A Felix

Detail Information

Publications7

  1. 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+)...
  2. 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)...
  3. 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...
  4. 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...
  5. 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...
  6. 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...