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Grant Details

Grant Number: 5R01CA134674-04 Interpret this number
Primary Investigator: Camp, Nicola
Organization: University Of Utah
Project Title: Genetic Epidemiology of Chronic Lymphocytic Leukemia
Fiscal Year: 2013
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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

Genetic risk factors in two Utah pedigrees at high risk for suicide.
Authors: Coon H, Darlington T, Pimentel R, Smith KR, Huff CD, Hu H, Jerominski L, Hansen J, Klein M, Callor WB, Byrd J, Bakian A, Crowell SE, McMahon WM, Rajamanickam V, Camp NJ, McGlade E, Yurgelun-Todd D, Grey T, Gray D
Source: Transl Psychiatry, 2013 Nov 19;3, p. e325.
EPub date: 2013 Nov 19.
PMID: 24252905
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
Authors: Berndt SI, Skibola CF, Joseph V, Camp NJ, Nieters A, Wang Z, Cozen W, Monnereau A, Wang SS, Kelly RS, Lan Q, Teras LR, Chatterjee N, Chung CC, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, Birmann BM, Armstrong BK, Cocco P, Zhang Y, Severi G, Zeleniuch-Jacquotte A, Lawrence C, Burdette L, Yuenger J, Hutchinson A, Jacobs KB, Call TG, Shanafelt TD, Novak AJ, Kay NE, Liebow M, Wang AH, Smedby KE, Adami HO, Melbye M, Glimelius B, Chang ET, Glenn M, Curtin K, Cannon-Albright LA, Jones B, Diver WR, Link BK, Weiner GJ, Conde L, Bracci PM, Riby J, Holly EA, Smith MT, Jackson RD, Tinker LF, Benavente Y, Becker N, Boffetta P, Brennan P, Foretova L, Maynadie M, McKay J, Staines A, Rabe KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Lanasa MC, Spector LG, Leis JF, Cunningham JM, Weinberg JB, Morrison VA, Caporaso NE, Norman AD, Linet MS, De Roos AJ, Morton LM, Severson RK, Riboli E, Vineis P, Kaaks R, Trichopoulos D, Masala G, Weiderpass E, Chirlaque MD, Vermeulen RC, Travis RC, Giles GG, Albanes D, Virtamo J, Weinstein S, Clavel J, Zheng T, Holford TR, Offit K, Zelenetz A, Klein RJ, Spinelli JJ, Bertrand KA, Laden F, Giovannucci E, Kraft P, Kricker A, Turner J, Vajdic CM, Ennas MG, Ferri GM, Miligi L, Liang L, Sampson J, Crouch S, Park JH, North KE, Cox A, Snowden JA, Wright J, Carracedo A, Lopez-Otin C, Bea S, Salaverria I, Martin-Garcia D, Campo E, Fraumeni JF Jr, de Sanjose S, Hjalgrim H, Cerhan JR, Chanock SJ, Rothman N, Slager SL
Source: Nat Genet, 2013 Aug;45(8), p. 868-76.
EPub date: 2013 Jun 16.
PMID: 23770605
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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 JM, Cannon-Albright LA, Camp NJ
Source: BMC Genomics, 2012 Nov 28;13, p. 676.
EPub date: 2012 Nov 28.
PMID: 23190577
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A family-based paradigm to identify candidate chromosomal regions for isolated congenital diaphragmatic hernia.
Authors: Arrington CB, Bleyl SB, Matsunami N, Bowles NE, Leppert TI, Demarest BL, Osborne K, Yoder BA, Byrne JL, Schiffman JD, Null DM, DiGeronimo R, Rollins M, Faix R, Comstock J, Camp NJ, Leppert MF, Yost HJ, Brunelli L
Source: Am J Med Genet A, 2012 Dec;158A(12), p. 3137-47.
EPub date: 2012 Nov 19.
PMID: 23165927
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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 SL, Camp NJ, Conde L, Shanafelt TD, Achenbach SJ, Rabe KG, Kay NE, Novak AJ, Call TG, Bracci PM, Sille FM, Sanchez S, Akers NK, Cunningham JM, Serie DJ, McDonnell SK, Leis JF, Wang AH, Weinberg JB, Glenn M, Link B, Vachon CM, Lanasa MC, Skibola CF, Cerhan JR
Source: Br J Haematol, 2012 Dec;159(5), p. 572-6.
EPub date: 2012 Oct 1.
PMID: 23025533
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Shared genomic segment analysis: the power to find rare disease variants.
Authors: Knight S, Abo RP, Abel HJ, Neklason DW, Tuohy TM, Burt RW, Thomas A, Camp NJ
Source: Ann Hum Genet, 2012 Nov;76(6), p. 500-9.
EPub date: 2012 Sep 19.
PMID: 22989048
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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 NJ
Source: BMC Proc, 2011 Nov 29;5 Suppl 9, p. S9.
EPub date: 2011 Nov 29.
PMID: 22373081
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Fine-mapping CASP8 risk variants in breast cancer.
Authors: Camp NJ, Parry M, Knight S, Abo R, Elliott G, Rigas SH, Balasubramanian SP, Reed MW, McBurney H, Latif A, Newman WG, Cannon-Albright LA, Evans DG, Cox A
Source: Cancer Epidemiol Biomarkers Prev, 2012 Jan;21(1), p. 176-81.
EPub date: 2011 Nov 4.
PMID: 22056502
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Identification of regions of positive selection using Shared Genomic Segment analysis.
Authors: Cai Z, Camp NJ, Cannon-Albright L, Thomas A
Source: Eur J Hum Genet, 2011 Jun;19(6), p. 667-71.
EPub date: 2011 Feb 9.
PMID: 21304558
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Haplotype association analyses in resources of mixed structure using Monte Carlo testing.
Authors: Abo R, Wong J, Thomas A, Camp NJ
Source: BMC Bioinformatics, 2010 Dec 9;11, p. 592.
EPub date: 2010 Dec 9.
PMID: 21143908
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