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Grant Details

Grant Number: 5R01CA122663-05 Interpret this number
Primary Investigator: Skibola, Christine
Organization: University Of California Berkeley
Project Title: A Genome-Wide Association Study of Non-Hodgkin Lymphoma
Fiscal Year: 2010
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Abstract

DESCRIPTION (provided by applicant): Incidence rates of non-Hodgkin lymphoma (NHL) have increased dramatically in the U.S. and other industrialized countries over the past 40 years, though reasons for this rise in rates are largely unexplained. In 2005, it has been estimated that NHL will account for 56,390 newly diagnosed cases and 19,200 associated deaths. Family and population-based studies provide evidence that genetic susceptibility plays a role in lymphomagenesis. However, the contribution of common genetic alleles and gene-environment interactions needs further investigation. Using Perlegen high-density oligonucleotide arrays, genome-wide genotyping on pooled DNA will be conducted to screen for NHL susceptibility markers. 267,000 haplotype tagging single nucleotide polymorphisms (SNPs) will be evaluated that span the genome on DNA pools from 1,000 NHL cases and 1,000 controls in a large population-based case-control study in the San Francisco Bay Area (recruitment of 2,000 cases and 2,000 controls to be completed in Spring 2006). Over 1,400 cases and 1,400 controls already have been ascertained with extensive epidemiological information collected from all study participants. Once target genes are identified by pooled genotyping, the association of these loci with NHL risk will be verified and further investigated by individual genotyping. An additional 7,000 SNPs will be individually genotyped in the human leukocyte antigen (HLA) region to investigate the involvement of HLA loci in the pathogenesis of NHL. Positive findings will be replicated in a second set of 1,000 NHL cases and 1,000 controls. Fine mapping genotyping will be performed on confirmed genes of interest. To add an additional replication step, another approximately 400 NHL cases and 800 controls from a previous NHL study (based in the San Francisco Bay Area) will be genotyped. This study, which constitutes one of the largest case-control NHL genetic epidemiology studies conducted to date, will broaden our current understanding of important mechanistic pathways involved in lymphomagenesis. Furthermore, these results may be translated to NHL screening, prevention or treatment regimens. The data generated from this study will provide a framework for further investigation within the NHL consortium, InterLymph. Results will later be combined with that from other InterLymph case-control studies in pooled analyses.

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Publications

Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development.
Authors: Schuetz JM, Daley D, Leach S, Conde L, Berry BR, Gallagher RP, Connors JM, Gascoyne RD, Bracci PM, Skibola CF, Spinelli JJ, Brooks-Wilson AR
Source: PLoS One, 2013;8(9), p. e75170.
EPub date: 2013 Sep 30.
PMID: 24098683
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Coding variants at hexa-allelic amino acid 13 of HLA-DRB1 explain independent SNP associations with follicular lymphoma risk.
Authors: Foo JN, Smedby KE, Akers NK, Berglund M, Irwan ID, Jia X, Li Y, Conde L, Darabi H, Bracci PM, Melbye M, Adami HO, Glimelius B, Khor CC, Hjalgrim H, Padyukov L, Humphreys K, Enblad G, Skibola CF, de Bakker PI, Liu J
Source: Am J Hum Genet, 2013 Jul 11;93(1), p. 167-72.
EPub date: 2013 Jun 20.
PMID: 23791106
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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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Integrating GWAS and expression data for functional characterization of disease-associated SNPs: an application to follicular lymphoma.
Authors: Conde L, Bracci PM, Richardson R, Montgomery SB, Skibola CF
Source: Am J Hum Genet, 2013 Jan 10;92(1), p. 126-30.
EPub date: 2012 Dec 13.
PMID: 23246294
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PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium.
Authors: Nieters A, Conde L, Slager SL, Brooks-Wilson A, Morton L, Skibola DR, Novak AJ, Riby J, Ansell SM, Halperin E, Shanafelt TD, Agana L, Wang AH, De Roos AJ, Severson RK, Cozen W, Spinelli J, Butterbach K, Becker N, de Sanjose S, Benavente Y, Cocco P, Staines A, Maynadié M, Foretova L, Boffetta P, Brennan P, Lan Q, Zhang Y, Zheng T, Purdue M, Armstrong B, Kricker A, Vajdic CM, Grulich A, Smith MT, Bracci PM, Chanock SJ, Hartge P, Cerhan JR, Wang SS, Rothman N, Skibola CF
Source: Blood, 2012 Nov 29;120(23), p. 4645-8.
EPub date: 2012 Oct 9.
PMID: 23047821
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A meta-analysis of genome-wide association studies of follicular lymphoma.
Authors: Skibola CF, Conde L, Foo JN, Riby J, Humphreys K, Sillé FC, Darabi H, Sanchez S, Hjalgrim H, Liu J, Bracci PM, Smedby KE
Source: BMC Genomics, 2012 Oct 1;13, p. 516.
EPub date: 2012 Oct 1.
PMID: 23025665
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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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Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia.
Authors: Slager SL, Skibola CF, Di Bernardo MC, Conde L, Broderick P, McDonnell SK, Goldin LR, Croft N, Holroyd A, Harris S, Riby J, Serie DJ, Kay NE, Call TG, Bracci PM, Halperin E, Lanasa MC, Cunningham JM, Leis JF, Morrison VA, Spector LG, Vachon CM, Shanafelt TD, Strom SS, Camp NJ, Weinberg JB, Matutes E, Caporaso NE, Wade R, Dyer MJ, Dearden C, Cerhan JR, Catovsky D, Houlston RS
Source: Blood, 2012 Jul 26;120(4), p. 843-6.
EPub date: 2012 Jun 13.
PMID: 22700719
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Multi-locus HLA class I and II allele and haplotype associations with follicular lymphoma.
Authors: Skibola CF, Akers NK, Conde L, Ladner M, Hawbecker SK, Cohen F, Ribas F, Erlich HA, Goodridge D, Trachtenberg EA, Smith MT, Bracci PM
Source: Tissue Antigens, 2012 Apr;79(4), p. 279-86.
EPub date: 2012 Feb 2.
PMID: 22296171
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Post-GWAS functional characterization of susceptibility variants for chronic lymphocytic leukemia.
Authors: Sillé FC, Thomas R, Smith MT, Conde L, Skibola CF
Source: PLoS One, 2012;7(1), p. e29632.
EPub date: 2012 Jan 3.
PMID: 22235315
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The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma.
Authors: Carvalho A, Cunha C, Almeida AJ, Osório NS, Saraiva M, Teixeira-Coelho M, Pedreiro S, Torrado E, Domingues N, Gomes-Alves AG, Marques A, Lacerda JF, da Silva MG, Gomes M, Pinto AC, Torres F, Rendeiro P, Tavares P, Di Ianni M, Medeiros R, Heutink P, Bracci PM, Conde L, Ludovico P, Pedrosa J, Maciel P, Pitzurra L, Aversa F, Marques H, Paiva A, Skibola CF, Romani L, Castro AG, Rodrigues F
Source: Genes Immun, 2012 Feb;13(2), p. 197-201.
EPub date: 2011 Aug 25.
PMID: 21866115
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Multiplexed, ligation-dependent probe amplification for rapid and inexpensive HLA-DQB1 allelotyping.
Authors: Akers NK, Curry JD, Smith MT, Bracci PM, Skibola CF
Source: Tissue Antigens, 2011 Oct;78(4), p. 275-80.
EPub date: 2011 Jul 18.
PMID: 21762399
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A search for overlapping genetic susceptibility loci between non-Hodgkin lymphoma and autoimmune diseases.
Authors: Conde L, Bracci PM, Halperin E, Skibola CF
Source: Genomics, 2011 Jul;98(1), p. 9-14.
EPub date: 2011 Mar 23.
PMID: 21439368
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SNP rs6457327 in the HLA region on chromosome 6p is predictive of the transformation of follicular lymphoma.
Authors: Wrench D, Leighton P, Skibola CF, Conde L, Cazier JB, Matthews J, Iqbal S, Carlotti E, Bödör C, Montoto S, Calaminici M, Gribben JG, Lister TA, Fitzgibbon J
Source: Blood, 2011 Mar 17;117(11), p. 3147-50.
EPub date: 2011 Jan 13.
PMID: 21233317
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Association of HLA-DQB1 alleles with risk of follicular lymphoma.
Authors: Akers NK, Curry JD, Conde L, Bracci PM, Smith MT, Skibola CF
Source: Leuk Lymphoma, 2011 Jan;52(1), p. 53-8.
EPub date: 2010 Dec 6.
PMID: 21133715
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A generic coalescent-based framework for the selection of a reference panel for imputation.
Authors: Pa?aniuc B, Avinery R, Gur T, Skibola CF, Bracci PM, Halperin E
Source: Genet Epidemiol, 2010 Dec;34(8), p. 773-82.
PMID: 21058333
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Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32.
Authors: Conde L, Halperin E, Akers NK, Brown KM, Smedby KE, Rothman N, Nieters A, Slager SL, Brooks-Wilson A, Agana L, Riby J, Liu J, Adami HO, Darabi H, Hjalgrim H, Low HQ, Humphreys K, Melbye M, Chang ET, Glimelius B, Cozen W, Davis S, Hartge P, Morton LM, Schenk M, Wang SS, Armstrong B, Kricker A, Milliken S, Purdue MP, Vajdic CM, Boyle P, Lan Q, Zahm SH, Zhang Y, Zheng T, Becker N, Benavente Y, Boffetta P, Brennan P, Butterbach K, Cocco P, Foretova L, Maynadié M, de Sanjosé S, Staines A, Spinelli JJ, Achenbach SJ, Call TG, Camp NJ, Glenn M, Caporaso NE, Cerhan JR, Cunningham JM, Goldin LR, Hanson CA, Kay NE, Lanasa MC, Leis JF, Marti GE, Rabe KG, Rassenti LZ, Spector LG, Strom SS, Vachon CM, Weinberg JB, Holly EA, Chanock S, Smith MT, Bracci PM, Skibola CF
Source: Nat Genet, 2010 Aug;42(8), p. 661-4.
EPub date: 2010 Jul 18.
PMID: 20639881
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A functional TNFRSF5 polymorphism and risk of non-Hodgkin lymphoma, a pooled analysis.
Authors: Nieters A, Bracci PM, de Sanjosé S, Becker N, Maynadié M, Benavente Y, Foretova L, Cocco P, Staines A, Holly EA, Boffetta P, Brennan P, Skibola CF
Source: Int J Cancer, 2011 Mar 15;128(6), p. 1481-5.
PMID: 20473910
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Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of non-Hodgkin lymphoma in the InterLymph Consortium.
Authors: Skibola CF, Bracci PM, Nieters A, Brooks-Wilson A, de Sanjosé S, Hughes AM, Cerhan JR, Skibola DR, Purdue M, Kane E, Lan Q, Foretova L, Schenk M, Spinelli JJ, Slager SL, De Roos AJ, Smith MT, Roman E, Cozen W, Boffetta P, Kricker A, Zheng T, Lightfoot T, Cocco P, Benavente Y, Zhang Y, Hartge P, Linet MS, Becker N, Brennan P, Zhang L, Armstrong B, Smith A, Shiao R, Novak AJ, Maynadie M, Chanock SJ, Staines A, Holford TR, Holly EA, Rothman N, Wang SS
Source: Am J Epidemiol, 2010 Feb 1;171(3), p. 267-76.
EPub date: 2010 Jan 4.
PMID: 20047977
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Chemokine polymorphisms and lymphoma: a pooled analysis.
Authors: Bracci PM, Skibola CF, Conde L, Halperin E, Lightfoot T, Smith A, Paynter RA, Skibola DR, Agana L, Roman E, Kane E, Wiencke JK
Source: Leuk Lymphoma, 2010 Mar;51(3), p. 497-506.
PMID: 20038229
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Genetic variants at 6p21.33 are associated with susceptibility to follicular lymphoma.
Authors: Skibola CF, Bracci PM, Halperin E, Conde L, Craig DW, Agana L, Iyadurai K, Becker N, Brooks-Wilson A, Curry JD, Spinelli JJ, Holly EA, Riby J, Zhang L, Nieters A, Smith MT, Brown KM
Source: Nat Genet, 2009 Aug;41(8), p. 873-5.
EPub date: 2009 Jul 20.
PMID: 19620980
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Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma.
Authors: Skibola CF, Bracci PM, Halperin E, Nieters A, Hubbard A, Paynter RA, Skibola DR, Agana L, Becker N, Tressler P, Forrest MS, Sankararaman S, Conde L, Holly EA, Smith MT
Source: PLoS One, 2008 Jun 30;3(7), p. e2816.
EPub date: 2008 Jun 30.
PMID: 18636124
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A functional TNFRSF5 gene variant is associated with risk of lymphoma.
Authors: Skibola CF, Nieters A, Bracci PM, Curry JD, Agana L, Skibola DR, Hubbard A, Becker N, Smith MT, Holly EA
Source: Blood, 2008 Apr 15;111(8), p. 4348-54.
EPub date: 2008 Feb 20.
PMID: 18287517
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Obesity, diet and risk of non-Hodgkin lymphoma.
Authors: Skibola CF
Source: Cancer Epidemiol Biomarkers Prev, 2007 Mar;16(3), p. 392-5.
EPub date: 2007 Mar 2.
PMID: 17337642
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