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National Institutes of Health: National Cancer Institute: Division of Cancer Control and Population Sciences
Grant Details

Grant Number: 5R01CA079940-08 Interpret this number
Primary Investigator: Ross, Julie
Organization: University Of Minnesota
Project Title: Epidemiology of Infant Leukemia
Fiscal Year: 2007
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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).

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Publications

Excess Congenital Non-synonymous Variation In Leukemia-associated Genes In Mll- Infant Leukemia: A Children's Oncology Group Report
Authors: Valentine M.C. , Linabery A.M. , Chasnoff S. , Hughes A.E. , Mallaney C. , Sanchez N. , Giacalone J. , Heerema N.A. , Hilden J.M. , Spector L.G. , et al. .
Source: Leukemia, 2014 Jun; 28(6), p. 1235-41.
PMID: 24301523
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Self-report Versus Medical Record - Perinatal Factors In A Study Of Infant Leukaemia: A Study From The Children's Oncology Group
Authors: Jurek A.M. , Greenland S. , Spector L.G. , Roesler M.A. , Robison L.L. , Ross J.A. .
Source: Paediatric And Perinatal Epidemiology, 2011 Nov; 25(6), p. 540-8.
PMID: 21980943
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Maternal Prenatal Cigarette, Alcohol And Illicit Drug Use And Risk Of Infant Leukaemia: A Report From The Children's Oncology Group
Authors: Slater M.E. , Linabery A.M. , Blair C.K. , Spector L.G. , Heerema N.A. , Robison L.L. , Ross J.A. .
Source: Paediatric And Perinatal Epidemiology, 2011 Nov; 25(6), p. 559-65.
PMID: 21980945
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Maternal Exposure To Household Chemicals And Risk Of Infant Leukemia: A Report From The Children's Oncology Group
Authors: Slater M.E. , Linabery A.M. , Spector L.G. , Johnson K.J. , Hilden J.M. , Heerema N.A. , Robison L.L. , Ross J.A. .
Source: Cancer Causes & Control : Ccc, 2011 Aug; 22(8), p. 1197-204.
PMID: 21691732
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Analgesic Use During Pregnancy And Risk Of Infant Leukaemia: A Children's Oncology Group Study
Authors: Ognjanovic S. , Blair C. , Spector L.G. , Robison L.L. , Roesler M. , Ross J.A. .
Source: British Journal Of Cancer, 2011-02-01 00:00:00.0; 104(3), p. 532-6.
PMID: 21157452
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Maternal Vitamin And Iron Supplementation And Risk Of Infant Leukaemia: A Report From The Children's Oncology Group
Authors: Linabery A.M. , Puumala S.E. , Hilden J.M. , Davies S.M. , Heerema N.A. , Roesler M.A. , Ross J.A. , Children's Oncology Group .
Source: British Journal Of Cancer, 2010-11-23 00:00:00.0; 103(11), p. 1724-8.
PMID: 20978510
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Infant Leukemia And Congenital Abnormalities: A Children's Oncology Group Study
Authors: Johnson K.J. , Roesler M.A. , Linabery A.M. , Hilden J.M. , Davies S.M. , Ross J.A. .
Source: Pediatric Blood & Cancer, 2010-07-15 00:00:00.0; 55(1), p. 95-9.
PMID: 20486175
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Comparability And Representativeness Of Control Groups In A Case-control Study Of Infant Leukemia: A Report From The Children's Oncology Group
Authors: Puumala S.E. , Spector L.G. , Robison L.L. , Bunin G.R. , Olshan A.F. , Linabery A.M. , Roesler M.A. , Blair C.K. , Ross J.A. .
Source: American Journal Of Epidemiology, 2009-08-01 00:00:00.0; 170(3), p. 379-87.
PMID: 19498073
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Environmental And Genetic Susceptibility To Mll-defined Infant Leukemia
Authors: Ross J.A. .
Source: Journal Of The National Cancer Institute. Monographs, 2008; (39), p. 83-6.
PMID: 18648010
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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 G.R. , Spector L.G. , Olshan A.F. , Robison L.L. , Roesler M. , Grufferman S. , Shu X.O. , Ross J.A. .
Source: American Journal Of Epidemiology, 2007-07-01 00:00:00.0; 166(1), p. 109-16.
PMID: 17456476
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Maternal Hemoglobin Concentration During Pregnancy And Risk Of Infant Leukaemia: A Children's Oncology Group Study
Authors: Peters A.M. , Blair C.K. , Verneris M.R. , Neglia J.P. , Robison L.L. , Spector L.G. , Reaman G.H. , Felix C.A. , Ross J.A. , Children's Oncology Group .
Source: British Journal Of Cancer, 2006-11-06 00:00:00.0; 95(9), p. 1274-6.
PMID: 17003777
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Maternal Diet And Infant Leukemia: The Dna Topoisomerase Ii Inhibitor Hypothesis: A Report From The Children's Oncology Group
Authors: Spector L.G. , Xie Y. , Robison L.L. , Heerema N.A. , Hilden J.M. , Lange B. , Felix C.A. , Davies S.M. , Slavin J. , Potter J.D. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2005 Mar; 14(3), p. 651-5.
PMID: 15767345
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Invited Commentary: Birth Certificates--a Best Control Scenario?
Authors: Ross J.A. , Spector L.G. , Olshan A.F. , Bunin G.R. .
Source: American Journal Of Epidemiology, 2004-05-15 00:00:00.0; 159(10), p. 922-4; discussion 925.
PMID: 15128602
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Prescription Medication Use During Pregnancy And Risk Of Infant Leukemia (united States)
Authors: Ross J.A. , Xie Y. , Davies S.M. , Shu X.O. , Pendergrass T.W. , Robison L.L. .
Source: Cancer Causes & Control : Ccc, 2003 Jun; 14(5), p. 447-51.
PMID: 12946039
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Diet And Risk Of Leukemia In The Iowa Women's Health Study
Authors: Ross J.A. , Kasum C.M. , Davies S.M. , Jacobs D.R. , Folsom A.R. , Potter J.D. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2002 Aug; 11(8), p. 777-81.
PMID: 12163333
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Vitamin K Prophylaxis And Childhood Cancer
Authors: Ross J.A. , Davies S.M. .
Source: Medical And Pediatric Oncology, 2000 Jun; 34(6), p. 434-7.
PMID: 10842253
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