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Grant Details

Grant Number: 5R01CA075169-05 Interpret this number
Primary Investigator: Ross, Julie
Organization: University Of Minnesota Twin Cities
Project Title: Epidemiology of Down Syndrome-Leukemia & Down Syndrome
Fiscal Year: 2001
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Abstract

DESCRIPTION: The environmental aetiology of Down syndrome (DS) is largely unknown. DS children are at nearly a 20-fold increased risk of developing leukemia compared to children in the general population. Trisomy 21 is also one of the most common acquired cytogenetic abnormalities in childhood leukemia. Thus, constitutional trisomy 21 may represent a first genetic event in the development of leukemia. Since only 1% of DS children ever develop leukemia, subsequent environmental exposures could be responsible for frank leukemia in this population. The proposed investigation will include: 1) children with DS, under the age of 19, diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), identified through the CCG; 2) children with DS, under the age of 19, frequency-matched by geographic region, age, and race to DS-leukemia cases; and 3) random-digit dialing (RDD) selected regional controls. The proposed case-control studies will include parental interviews, collection of cytogenetic and morphologic data, and medical record validation. In the first case-control study (DS-leukemia compared to DS without leukemia) the plan is to determine whether children with DS and leukemia share similar risk factors reported to be associated with childhood ALL and/or AML including maternal alcohol exposure during pregnancy, specific parental occupational exposures, maternal history of prior fetal loss, preconceptional and in utero exposure to X rays. Other potential risk factors will also be explored that may be unique to this case group, including childhood medical exposures, frequency of exposure to infections, vitamin supplementation, and maternal diet during pregnancy. In the second case-control study (DS compared to normal population), the plan is to investigate potential risk factors for DS, as epidemiologic investigations concerning the environmental aetiology of DS are limited. Specifically, the following risk factors, based on previous study findings, will be addressed: parental occupations and occupational exposures, parental smoking and alcohol use, prior use of specific contraceptives, family history of Alzheimer's disease, and parental preconception exposure to x-rays. The proposed study would utilize resources available through the CCG and would include: 1) 152 DS-leukemia cases diagnosed over a five-year period from 1/1/97 through 12/31/01 by the CCG; 2) 304 frequency-matched DS controls; and 3) 304 frequency matched RDD controls. It is claimed that each case-control study has adequate statistical power to address the hypotheses being explored.

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Publications

Maternal health conditions during pregnancy and acute leukemia in children with Down syndrome: A Children's Oncology Group study.
Authors: Ognjanovic S. , Puumala S. , Spector L.G. , Smith F.O. , Robison L.L. , Olshan A.F. , Ross J.A. .
Source: Pediatric blood & cancer, 2009 May; 52(5), p. 602-8.
PMID: 19148952
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Periconceptional maternal vitamin supplementation and childhood leukaemia: an uncertainty analysis.
Authors: Jurek A.M. , Maldonado G. , Spector L.G. , Ross J.A. .
Source: Journal of epidemiology and community health, 2009 Feb; 63(2), p. 168-72.
EPub date: 2008-10-31.
PMID: 18977808
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Congenital abnormalities and acute leukemia among children with Down syndrome: a Children's Oncology Group study.
Authors: Linabery A.M. , Blair C.K. , Gamis A.S. , Olshan A.F. , Heerema N.A. , Ross J.A. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008 Oct; 17(10), p. 2572-7.
EPub date: 2008-09-30.
PMID: 18829445
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Vitamin supplement use among children with Down's syndrome and risk of leukaemia: a Children's Oncology Group (COG) study.
Authors: Blair C.K. , Roesler M. , Xie Y. , Gamis A.S. , Olshan A.F. , Heerema N.A. , Robison L.L. , Ross J.A. , Children's Oncology Group (COG) .
Source: Paediatric and perinatal epidemiology, 2008 May; 22(3), p. 288-95.
PMID: 18426524
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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; 166(1), p. 109-16.
EPub date: 2007-04-23.
PMID: 17456476
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Exposure to medical test irradiation and acute leukemia among children with Down syndrome: a report from the Children's Oncology Group.
Authors: Linabery A.M. , Olshan A.F. , Gamis A.S. , Smith F.O. , Heerema N.A. , Blair C.K. , Ross J.A. , Children's Oncology Group .
Source: Pediatrics, 2006 Nov; 118(5), p. e1499-508.
EPub date: 2006-10-09.
PMID: 17030598
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Child and maternal household chemical exposure and the risk of acute leukemia in children with Down's syndrome: a report from the Children's Oncology Group.
Authors: Alderton L.E. , Spector L.G. , Blair C.K. , Roesler M. , Olshan A.F. , Robison L.L. , Ross J.A. .
Source: American journal of epidemiology, 2006-08-01; 164(3), p. 212-21.
EPub date: 2006-06-07.
PMID: 16760223
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Periconceptional vitamin useand leukemia risk in children with Down syndrome: a Children's Oncology Group study.
Authors: Ross J.A. , Blair C.K. , Olshan A.F. , Robison L.L. , Smith F.O. , Heerema N.A. , Roesler M. .
Source: Cancer, 2005-07-15; 104(2), p. 405-10.
PMID: 15952191
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Epidemiology of leukemia in children with Down syndrome.
Authors: Ross J.A. , Spector L.G. , Robison L.L. , Olshan A.F. .
Source: Pediatric blood & cancer, 2005 Jan; 44(1), p. 8-12.
PMID: 15390275
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Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group.
Authors: Canfield K.N. , Spector L.G. , Robison L.L. , Lazovich D. , Roesler M. , Olshan A.F. , Smith F.O. , Heerema N.A. , Barnard D.R. , Blair C.K. , et al. .
Source: British journal of cancer, 2004-11-29; 91(11), p. 1866-72.
PMID: 15520821
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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; 159(10), p. 922-4; discussion 925.
PMID: 15128602
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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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Prenatal epidemiology of pediatric tumors.
Authors: Ross J.A. , Swensen A.R. .
Source: Current oncology reports, 2000 May; 2(3), p. 234-41.
PMID: 11122848
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Dietary flavonoids and the MLL gene: A pathway to infant leukemia?
Authors: Ross J.A. .
Source: Proceedings of the National Academy of Sciences of the United States of America, 2000-04-25; 97(9), p. 4411-3.
PMID: 10781030
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Seasonal variations in the diagnosis of childhood cancer in the United States.
Authors: Ross J.A. , Severson R.K. , Swensen A.R. , Pollock B.H. , Gurney J.G. , Robison L.L. .
Source: British journal of cancer, 1999 Oct; 81(3), p. 549-53.
PMID: 10507784
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