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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 LG, Smith FO, Robison LL, Olshan AF, Ross JA
Source: Pediatr 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 AM, Maldonado G, Spector LG, Ross JA
Source: J Epidemiol Community Health, 2009 Feb;63(2), p. 168-72.
EPub date: 2008 Oct 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 AM, Blair CK, Gamis AS, Olshan AF, Heerema NA, Ross JA
Source: Cancer Epidemiol Biomarkers Prev, 2008 Oct;17(10), p. 2572-7.
EPub date: 2008 Sep 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 CK, Roesler M, Xie Y, Gamis AS, Olshan AF, Heerema NA, Robison LL, Ross JA, Children's Oncology Group (COG)
Source: Paediatr Perinat Epidemiol, 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 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.
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 AM, Olshan AF, Gamis AS, Smith FO, Heerema NA, Blair CK, Ross JA, Children's Oncology Group
Source: Pediatrics, 2006 Nov;118(5), p. e1499-508.
EPub date: 2006 Oct 9.
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 LE, Spector LG, Blair CK, Roesler M, Olshan AF, Robison LL, Ross JA
Source: Am J Epidemiol, 2006 Aug 1;164(3), p. 212-21.
EPub date: 2006 Jun 7.
PMID: 16760223
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Periconceptional vitamin useand leukemia risk in children with Down syndrome: a Children's Oncology Group study.
Authors: Ross JA, Blair CK, Olshan AF, Robison LL, Smith FO, Heerema NA, Roesler M
Source: Cancer, 2005 Jul 15;104(2), p. 405-10.
PMID: 15952191
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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 KN, Spector LG, Robison LL, Lazovich D, Roesler M, Olshan AF, Smith FO, Heerema NA, Barnard DR, Blair CK, Ross JA
Source: Br J Cancer, 2004 Nov 29;91(11), p. 1866-72.
PMID: 15520821
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Epidemiology of leukemia in children with Down syndrome.
Authors: Ross JA, Spector LG, Robison LL, Olshan AF
Source: Pediatr Blood Cancer, 2005 Jan;44(1), p. 8-12.
PMID: 15390275
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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.
PMID: 15128602
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Prenatal epidemiology of pediatric tumors.
Authors: Ross JA, Swensen AR
Source: Curr Oncol Rep, 2000 May;2(3), p. 234-41.
PMID: 11122848
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Vitamin K prophylaxis and childhood cancer.
Authors: Ross JA, Davies SM
Source: Med Pediatr Oncol, 2000 Jun;34(6), p. 434-7.
PMID: 10842253
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Seasonal variations in the diagnosis of childhood cancer in the United States.
Authors: Ross JA, Severson RK, Swensen AR, Pollock BH, Gurney JG, Robison LL
Source: Br J Cancer, 1999 Oct;81(3), p. 549-53.
PMID: 10507784
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