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

Grant Number: 5R01CA134674-03 Interpret this number
Primary Investigator: Camp, Nicola
Organization: University Of Utah
Project Title: Genetic Epidemiology of Chronic Lymphocytic Leukemia
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): Chronic Lymphocytic Leukemia (CLL) is a B-cell lymphoproliferative disorder primarily involving the bone marrow, blood and lymph nodes. CLL is the most common type of leukemia in adults and although median survival can be quite long, between 8-12 years, most eventually succumb to their disease. The evidence for a genetic component to CLL is compelling but remains unknown, and is likely complex. However, opportunities to identify underlying variants are apparent -both by varied and unique study and analysis designs and via collaborative efforts. The research plan we propose is multifaceted, highly collaborative and includes several innovative techniques. We will pursue two study designs, each powerful to identify susceptibility genes with different underlying genetic models: high-risk pedigree-based shared genomic segment analysis and case- control association analyses. Genome-wide shared genomic segment analysis is a new method that requires extremely extended, high-risk pedigrees which are available only to researchers with genealogic resources, such as Utah. Our strategy for association will be both genome wide and candidate region. Ascertainment will involve two sites (Utah and Sheffield, UK) and will include both a discordant family-based element (Utah) and a population-based sample (UK). This approach exploits both the increased power of familial cases with the perspective of population-based samples. We are able to pursue these together due to software that we have developed. In addition to conventional analyses, we will develop new methods for the high-risk pedigree and case-control settings: homozygosity mapping in the high-risk pedigrees and case-control SGS and homozygosity mapping. Both conventional and novel methods will be performed as part of broader collaborative efforts. The resource that we will build is timely. CLL genetic research is still in its infancy. The concurrent development of these designs defines an extensive strategy for identifying regions of the genome harboring CLL susceptibility genes and will afford us the opportunity to play a significant role in shaping the direction of CLL genetic research. Particularly, Utah pedigrees, through their structure and high-risk nature, add a previously unrealized aspect to the global picture. If one design or collaborative effort can identify even a single susceptibility gene for CLL, we will have made an important and critical discovery in the etiology of CLL. Such a discovery would not only help our understanding of the etiology of CLL, but also may provide information about other lymphoproliferative disorders and may translate to other cancers.

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Publications

Haplotype Association Analyses In Resources Of Mixed Structure Using Monte Carlo Testing
Authors: Abo R. , Wong J. , Thomas A. , Camp N.J. .
Source: Bmc Bioinformatics, 2010; 11, p. 592.
PMID: 21143908
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Identification Of Regions Of Positive Selection Using Shared Genomic Segment Analysis
Authors: Cai Z. , Camp N.J. , Cannon-Albright L. , Thomas A. .
Source: European Journal Of Human Genetics : Ejhg, 2011 Jun; 19(6), p. 667-71.
PMID: 21304558
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Fine-mapping Casp8 Risk Variants In Breast Cancer
Authors: Camp N.J. , Parry M. , Knight S. , Abo R. , Elliott G. , Rigas S.H. , Balasubramanian S.P. , Reed M.W. , McBurney H. , Latif A. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2012 Jan; 21(1), p. 176-81.
PMID: 22056502
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Pairwise Shared Genomic Segment Analysis In High-risk Pedigrees: Application To Genetic Analysis Workshop 17 Exome-sequencing Snp Data
Authors: Cai Z. , Knight S. , Thomas A. , Camp N.J. .
Source: Bmc Proceedings, 2011; 5 Suppl 9, p. S9.
PMID: 22373081
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Shared Genomic Segment Analysis: The Power To Find Rare Disease Variants
Authors: Knight S. , Abo R.P. , Abel H.J. , Neklason D.W. , Tuohy T.M. , Burt R.W. , Thomas A. , Camp N.J. .
Source: Annals Of Human Genetics, 2012 Nov; 76(6), p. 500-9.
PMID: 22989048
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Common Variants Within 6p21.31 Locus Are Associated With Chronic Lymphocytic Leukaemia And, Potentially, Other Non-hodgkin Lymphoma Subtypes
Authors: Slager S.L. , Camp N.J. , Conde L. , Shanafelt T.D. , Achenbach S.J. , Rabe K.G. , Kay N.E. , Novak A.J. , Call T.G. , Bracci P.M. , et al. .
Source: British Journal Of Haematology, 2012 Dec; 159(5), p. 572-6.
PMID: 23025533
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A Family-based Paradigm To Identify Candidate Chromosomal Regions For Isolated Congenital Diaphragmatic Hernia
Authors: Arrington C.B. , Bleyl S.B. , Matsunami N. , Bowles N.E. , Leppert T.I. , Demarest B.L. , Osborne K. , Yoder B.A. , Byrne J.L. , Schiffman J.D. , et al. .
Source: American Journal Of Medical Genetics. Part A, 2012 Dec; 158A(12), p. 3137-47.
PMID: 23165927
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Pairwise Shared Genomic Segment Analysis In Three Utah High-risk Breast Cancer Pedigrees
Authors: Cai Z. , Thomas A. , Teerlink C. , Farnham J.M. , Cannon-Albright L.A. , Camp N.J. .
Source: Bmc Genomics, 2012; 13, p. 676.
PMID: 23190577
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Genome-wide Association Study Identifies Multiple Risk Loci For Chronic Lymphocytic Leukemia
Authors: Berndt S.I. , Skibola C.F. , Joseph V. , Camp N.J. , Nieters A. , Wang Z. , Cozen W. , Monnereau A. , Wang S.S. , Kelly R.S. , et al. .
Source: Nature Genetics, 2013 Aug; 45(8), p. 868-76.
PMID: 23770605
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Genetic Risk Factors In Two Utah Pedigrees At High Risk For Suicide
Authors: Coon H. , Darlington T. , Pimentel R. , Smith K.R. , Huff C.D. , Hu H. , Jerominski L. , Hansen J. , Klein M. , Callor W.B. , et al. .
Source: Translational Psychiatry, 2013; 3, p. e325.
PMID: 24252905
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Genome-wide Association Study Identifies Variants At 16p13 Associated With Survival In Multiple Myeloma Patients
Authors: Ziv E. , Dean E. , Hu D. , Martino A. , Serie D. , Curtin K. , Campa D. , Aftab B. , Bracci P. , Buda G. , et al. .
Source: Nature Communications, 2015; 6, p. 7539.
PMID: 26198393
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Meta-analysis Of Genome-wide Association Studies Discovers Multiple Loci For Chronic Lymphocytic Leukemia
Authors: Berndt S.I. , Camp N.J. , Skibola C.F. , Vijai J. , Wang Z. , Gu J. , Nieters A. , Kelly R.S. , Smedby K.E. , Monnereau A. , et al. .
Source: Nature Communications, 2016; 7, p. 10933.
PMID: 26956414
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Genetically Predicted Longer Telomere Length Is Associated With Increased Risk Of B-cell Lymphoma Subtypes
Authors: Machiela M.J. , Lan Q. , Slager S.L. , Vermeulen R.C. , Teras L.R. , Camp N.J. , Cerhan J.R. , Spinelli J.J. , Wang S.S. , Nieters A. , et al. .
Source: Human Molecular Genetics, 2016-04-15 00:00:00.0; 25(8), p. 1663-76.
PMID: 27008888
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