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Grant Details

Grant Number: 5R03CA125823-02 Interpret this number
Primary Investigator: Buffler, Patricia
Organization: University Of California Berkeley
Project Title: Mhc Genetic Variation, Exposure to Infections and Risk of Childhood Leukemia
Fiscal Year: 2008


Abstract

DESCRIPTION (provided by applicant): Childhood leukemia is the leading cause of cancer death among children and its causes are largely unknown. Acute lymphoblastic leukemia (ALL) accounts for approximately 80% of all pediatric leukemias. There is growing evidence supporting a role for immunologic mechanisms in the etiology of childhood leukemia and, more specifically, evidence to support an association of specific human leukocyte antigen (HLA) genes with the susceptibility to, or protection from, childhood leukemia, particularly ALL. The proposed study presents a unique opportunity to cost-effectively examine the major histocompatibility complex (MHC), a ~3.6 megabase pair region dense in genes involved in the immune system, including the functional human leukocyte antigen (HLA) class I and class II genes. Implementing the most recent molecular genetic techniques and statistical analytic methods, existing biologic and epidemiologic data will be utilized from the ongoing Northern California Childhood Leukemia Study, one of the most extensive population-based case-control studies of childhood leukemia in the United States. As an initial step towards identifying potentially important regions of the MHC in childhood ALL, a comprehensive screen of the MHC region using a specialized set of microsatellite markers will be conducted. This effort will be accompanied by targeted allelic typing of HLA-DP genes, particularly the HLA-DPB1 locus, which was shown to be strongly associated with childhood ALL in two independent population-based United Kingdom studies. The proposed study will examine the HLA-DP genes on risk of childhood ALL in two major ethnic groups in the United States, Hispanics and non-Hispanic Whites, and will evaluate whether this risk is modified by infectious exposures. An examination of HLA-DP genetic variation in concert with infectious exposures could yield uniquely informative clues as to the underlying immune-related biological mechanism of childhood ALL.



Publications

SNP association mapping across the extended major histocompatibility complex and risk of B-cell precursor acute lymphoblastic leukemia in children.
Authors: Urayama K.Y. , Chokkalingam A.P. , Metayer C. , Hansen H. , May S. , Ramsay P. , Wiemels J.L. , Wiencke J.K. , Trachtenberg E. , Thompson P. , et al. .
Source: PloS one, 2013; 8(8), p. e72557.
EPub date: 2013-08-22.
PMID: 23991122
Related Citations

HLA-DP genetic variation, proxies for early life immune modulation and childhood acute lymphoblastic leukemia risk.
Authors: Urayama K.Y. , Chokkalingam A.P. , Metayer C. , Ma X. , Selvin S. , Barcellos L.F. , Wiemels J.L. , Wiencke J.K. , Taylor M. , Brennan P. , et al. .
Source: Blood, 2012-10-11; 120(15), p. 3039-47.
EPub date: 2012-08-24.
PMID: 22923493
Related Citations

Early life exposure to infections and risk of childhood acute lymphoblastic leukemia.
Authors: Urayama K.Y. , Ma X. , Selvin S. , Metayer C. , Chokkalingam A.P. , Wiemels J.L. , Does M. , Chang J. , Wong A. , Trachtenberg E. , et al. .
Source: International journal of cancer, 2011-04-01; 128(7), p. 1632-43.
EPub date: 2010-12-17.
PMID: 21280034
Related Citations

The human major histocompatibility complex and childhood leukemia: an etiological hypothesis based on molecular mimicry.
Authors: Taylor M. , Hussain A. , Urayama K. , Chokkalingam A. , Thompson P. , Trachtenberg E. , Buffler P. .
Source: Blood cells, molecules & diseases, 2009 Mar-Apr; 42(2), p. 129-35.
EPub date: 2008-12-02.
PMID: 19054700
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