|Grant Number:||5R01CA079940-08 Interpret this number|
|Primary Investigator:||Ross, Julie|
|Organization:||University Of Minnesota|
|Project Title:||Epidemiology of Infant Leukemia|
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).
Excess congenital non-synonymous variation in leukemia-associated genes in MLL- infant leukemia: a Children's Oncology Group report.
Authors: Valentine MC, Linabery AM, Chasnoff S, Hughes AE, Mallaney C, Sanchez N, Giacalone J, Heerema NA, Hilden JM, Spector LG, Ross JA, Druley TE
Source: Leukemia, 2014 Jun;28(6), p. 1235-41.
EPub date: 2013 Dec 4.
Maternal prenatal cigarette, alcohol and illicit drug use and risk of infant leukaemia: a report from the Children's Oncology Group.
Authors: Slater ME, Linabery AM, Blair CK, Spector LG, Heerema NA, Robison LL, Ross JA
Source: Paediatr Perinat Epidemiol, 2011 Nov;25(6), p. 559-65.
EPub date: 2011 Aug 10.
Self-report versus medical record - perinatal factors in a study of infant leukaemia: a study from the Children's Oncology Group.
Authors: Jurek AM, Greenland S, Spector LG, Roesler MA, Robison LL, Ross JA
Source: Paediatr Perinat Epidemiol, 2011 Nov;25(6), p. 540-8.
EPub date: 2011 Aug 10.
Maternal exposure to household chemicals and risk of infant leukemia: a report from the Children's Oncology Group.
Authors: Slater ME, Linabery AM, Spector LG, Johnson KJ, Hilden JM, Heerema NA, Robison LL, Ross JA
Source: Cancer Causes Control, 2011 Aug;22(8), p. 1197-204.
EPub date: 2011 Jun 21.
Analgesic use during pregnancy and risk of infant leukaemia: a Children's Oncology Group study.
Authors: Ognjanovic S, Blair C, Spector LG, Robison LL, Roesler M, Ross JA
Source: Br J Cancer, 2011 Feb 1;104(3), p. 532-6.
EPub date: 2010 Dec 14.
Maternal vitamin and iron supplementation and risk of infant leukaemia: a report from the Children's Oncology Group.
Authors: Linabery AM, Puumala SE, Hilden JM, Davies SM, Heerema NA, Roesler MA, Ross JA, Children's Oncology Group
Source: Br J Cancer, 2010 Nov 23;103(11), p. 1724-8.
EPub date: 2010 Oct 26.
Infant leukemia and congenital abnormalities: a Children's Oncology Group study.
Authors: Johnson KJ, Roesler MA, Linabery AM, Hilden JM, Davies SM, Ross JA
Source: Pediatr Blood Cancer, 2010 Jul 15;55(1), p. 95-9.
Comparability and representativeness of control groups in a case-control study of infant leukemia: a report from the Children's Oncology Group.
Authors: Puumala SE, Spector LG, Robison LL, Bunin GR, Olshan AF, Linabery AM, Roesler MA, Blair CK, Ross JA
Source: Am J Epidemiol, 2009 Aug 1;170(3), p. 379-87.
EPub date: 2009 Jun 4.
Environmental and genetic susceptibility to MLL-defined infant leukemia.
Authors: Ross JA
Source: J Natl Cancer Inst Monogr, 2008;null(39), p. 83-6.
Secular trends in response rates for controls selected by random digit dialing in childhood cancer studies: a report from the Children's Oncology Group.
Authors: Bunin GR, Spector LG, Olshan AF, Robison LL, Roesler M, Grufferman S, Shu XO, Ross JA
Source: Am J Epidemiol, 2007 Jul 1;166(1), p. 109-16.
EPub date: 2007 Apr 23.
Maternal hemoglobin concentration during pregnancy and risk of infant leukaemia: a children's oncology group study.
Authors: Peters AM, Blair CK, Verneris MR, Neglia JP, Robison LL, Spector LG, Reaman GH, Felix CA, Ross JA, Children's Oncology Group
Source: Br J Cancer, 2006 Nov 6;95(9), p. 1274-6.
EPub date: 2006 Sep 26.
Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.
Authors: Spector LG, Xie Y, Robison LL, Heerema NA, Hilden JM, Lange B, Felix CA, Davies SM, Slavin J, Potter JD, Blair CK, Reaman GH, Ross JA
Source: Cancer Epidemiol Biomarkers Prev, 2005 Mar;14(3), p. 651-5.
Invited commentary: Birth certificates--a best control scenario?
Authors: Ross JA, Spector LG, Olshan AF, Bunin GR
Source: Am J Epidemiol, 2004 May 15;159(10), p. 922-4; discussion 925.
Prescription medication use during pregnancy and risk of infant leukemia (United States).
Authors: Ross JA, Xie Y, Davies SM, Shu XO, Pendergrass TW, Robison LL
Source: Cancer Causes Control, 2003 Jun;14(5), p. 447-51.
Diet and risk of leukemia in the Iowa Women's Health Study.
Authors: Ross JA, Kasum CM, Davies SM, Jacobs DR, Folsom AR, Potter JD
Source: Cancer Epidemiol Biomarkers Prev, 2002 Aug;11(8), p. 777-81.
Vitamin K prophylaxis and childhood cancer.
Authors: Ross JA, Davies SM
Source: Med Pediatr Oncol, 2000 Jun;34(6), p. 434-7.