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Grant Details

Grant Number: 5R01CA104682-08 Interpret this number
Primary Investigator: Skibola, Christine
Organization: University Of California Berkeley
Project Title: Genetic Susceptibility to Non-Hodgkin Lymphoma
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): Genetic Susceptibility to Non-Hodgkin Lymphoma - Renewal: Dramatic increases worldwide in the incidence of non-Hodgkin lymphoma (NHL) have stimulated considerable efforts to identify factors that may aid in the prevention and treatment of this disease and to further our understanding of the biological mechanisms that initiate and sustain a lymphoid malignancy. As a continuation of grant R01 CA 104682-01, the overall goal of this proposal is to identify genetic variants that are causally related to risk of NHL using DNA from two large case-control studies based in the San Francisco Bay Area: SF Bay Area NHL1 (400 cases, 800 controls) and SF Bay Area NHL2 (1,800 cases, 1,800 controls). We have made considerable contributions to the field to date in identifying genetic risk factors of NHL in multiple studies. We have identified nearly thirty genes strongly associated with NHL during the previous grant period, from a recent genome scan and through collaborations within the International Consortium of Investigators Working on NHL Epidemiologic Studies (InterLymph). These genes lie in the obesity, inflammation, hormone production and innate immunity pathways. Now, using the Illumina genotyping platform, under Aim#1, we will fine map these genes to identify true NHL risk alleles. Under Aim#2, as part of ongoing replication studies within InterLymph, we will lead the fine mapping of genes associated with NHL based on a large pooled genetic study currently underway that is being spearheaded by Dr. Skibola. Using data from a recent genome scan, in Aim#3, we will assess the influence of copy number variation on risk of NHL, which will then be confirmed in our additional NHL cases and controls. Finally, we will test the function of putatively causal polymorphisms identified through Aims 1 and 2 and perform mechanistic studies of risk alleles to gain further insights that will enhance our current understanding of mechanisms involved in lymphomagenesis. Results from these studies 1) can be translated into prevention and treatment programs aimed at reducing the public health burden of NHL worldwide; 2) use already existing DNA from two NHL case-control studies; 3) use already existing data from our genome scan; 4) will be the first to report genetic susceptibility of NHL based on copy number variation in population studies; and 5) will support major efforts to perform replication, fine mapping and pooled analyses within the InterLymph consortium. PUBLIC HEALTH RELEVANCE: In 2008, non-Hodgkin lymphoma (NHL) will account for over 63,000 newly diagnosed cases and 20,000 associated deaths in the U.S. and over 300,000 cases and 172,000 deaths worldwide. Incidence and mortality rates have steadily increased over the last several decades, making NHL the fifth most common cancer in the U.S. An important role for family genetics has been established in causing lymphoma and common genetic variants may influence disease susceptibility. These studies will use genetics to increase our understanding of how lymphoma develops in the body and provide clues about environmental agents and lifestyle exposures that contribute to disease risk that may be translated to NHL screening, prevention and treatment programs.

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Publications

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF, Bracci PM, de Sanjosé S, Smedby KE, Chiu BC, Zhang Y, Mbulaiteye SM, Monnereau A, Turner JJ, Clavel J, Adami HO, Chang ET, Glimelius B, Hjalgrim H, Melbye M, Crosignani P, di Lollo S, Miligi L, Nanni O, Ramazzotti V, Rodella S, Costantini AS, Stagnaro E, Tumino R, Vindigni C, Vineis P, Becker N, Benavente Y, Boffetta P, Brennan P, Cocco P, Foretova L, Maynadié M, Nieters A, Staines A, Colt JS, Cozen W, Davis S, de Roos AJ, Hartge P, Rothman N, Severson RK, Holly EA, Call TG, Feldman AL, Habermann TM, Liebow M, Blair A, Cantor KP, Kane EV, Lightfoot T, Roman E, Smith A, Brooks-Wilson A, Connors JM, Gascoyne RD, Spinelli JJ, Armstrong BK, Kricker A, Holford TR, Lan Q, Zheng T, Orsi L, Dal Maso L, Franceschi S, La Vecchia C, Negri E, Serraino D, Bernstein L, Levine A, Friedberg JW, Kelly JL, Berndt SI, Birmann BM, Clarke CA, Flowers CR, Foran JM, Kadin ME, Paltiel O, Weisenburger DD, Linet MS, Sampson JN
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 130-44.
PMID: 25174034
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Medical history, lifestyle, family history, and occupational risk factors for adult acute lymphocytic leukemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Skibola CF, Slager SL, Berndt SI, Lightfoot T, Sampson JN, Morton LM, Weisenburger DD
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 125-9.
PMID: 25174033
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Medical history, lifestyle, and occupational risk factors for hairy cell leukemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Monnereau A, Slager SL, Hughes AM, Smith A, Glimelius B, Habermann TM, Berndt SI, Staines A, Norman AD, Cerhan JR, Sampson JN, Morton LM, Clavel J
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 115-24.
PMID: 25174032
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Medical history, lifestyle, family history, and occupational risk factors for sporadic Burkitt lymphoma/leukemia: the Interlymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Mbulaiteye SM, Morton LM, Sampson JN, Chang ET, Costas L, de Sanjosé S, Lightfoot T, Kelly J, Friedberg JW, Cozen W, Marcos-Gragera R, Slager SL, Birmann BM, Weisenburger DD
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 106-14.
PMID: 25174031
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Medical history, lifestyle, family history, and occupational risk factors for mycosis fungoides and Sézary syndrome: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Aschebrook-Kilfoy B, Cocco P, La Vecchia C, Chang ET, Vajdic CM, Kadin ME, Spinelli JJ, Morton LM, Kane EV, Sampson JN, Kasten C, Feldman AL, Wang SS, Zhang Y
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 98-105.
PMID: 25174030
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Medical history, lifestyle, family history, and occupational risk factors for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Vajdic CM, Landgren O, McMaster ML, Slager SL, Brooks-Wilson A, Smith A, Staines A, Dogan A, Ansell SM, Sampson JN, Morton LM, Linet MS
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 87-97.
PMID: 25174029
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Medical history, lifestyle, family history, and occupational risk factors for mantle cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Smedby KE, Sampson JN, Turner JJ, Slager SL, Maynadié M, Roman E, Habermann TM, Flowers CR, Berndt SI, Bracci PM, Hjalgrim H, Weisenburger DD, Morton LM
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 76-86.
PMID: 25174028
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Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM, Feldman AL, Lightfoot T, Boffetta P, Melbye M, Lan Q, Sampson JN, Morton LM, Zhang Y, Weisenburger DD
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 66-75.
PMID: 25174027
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Medical history, lifestyle, family history, and occupational risk factors for marginal zone lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Bracci PM, Benavente Y, Turner JJ, Paltiel O, Slager SL, Vajdic CM, Norman AD, Cerhan JR, Chiu BC, Becker N, Cocco P, Dogan A, Nieters A, Holly EA, Kane EV, Smedby KE, Maynadié M, Spinelli JJ, Roman E, Glimelius B, Wang SS, Sampson JN, Morton LM, de Sanjosé S
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 52-65.
PMID: 25174026
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Medical history, lifestyle, family history, and occupational risk factors for chronic lymphocytic leukemia/small lymphocytic lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Slager SL, Benavente Y, Blair A, Vermeulen R, Cerhan JR, Costantini AS, Monnereau A, Nieters A, Clavel J, Call TG, Maynadié M, Lan Q, Clarke CA, Lightfoot T, Norman AD, Sampson JN, Casabonne D, Cocco P, de Sanjosé S
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 41-51.
PMID: 25174025
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Medical history, lifestyle, family history, and occupational risk factors for follicular lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Linet MS, Vajdic CM, Morton LM, de Roos AJ, Skibola CF, Boffetta P, Cerhan JR, Flowers CR, de Sanjosé S, Monnereau A, Cocco P, Kelly JL, Smith AG, Weisenburger DD, Clarke CA, Blair A, Bernstein L, Zheng T, Miligi L, Clavel J, Benavente Y, Chiu BC
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 26-40.
PMID: 25174024
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Medical history, lifestyle, family history, and occupational risk factors for diffuse large B-cell lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.
Authors: Cerhan JR, Kricker A, Paltiel O, Flowers CR, Wang SS, Monnereau A, Blair A, Dal Maso L, Kane EV, Nieters A, Foran JM, Miligi L, Clavel J, Bernstein L, Rothman N, Slager SL, Sampson JN, Morton LM, Skibola CF
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 15-25.
PMID: 25174023
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Rationale and Design of the International Lymphoma Epidemiology Consortium (InterLymph) Non-Hodgkin Lymphoma Subtypes Project.
Authors: Morton LM, Sampson JN, Cerhan JR, Turner JJ, Vajdic CM, Wang SS, Smedby KE, de Sanjosé S, Monnereau A, Benavente Y, Bracci PM, Chiu BC, Skibola CF, Zhang Y, Mbulaiteye SM, Spriggs M, Robinson D, Norman AD, Kane EV, Spinelli JJ, Kelly JL, La Vecchia C, Dal Maso L, Maynadié M, Kadin ME, Cocco P, Costantini AS, Clarke CA, Roman E, Miligi L, Colt JS, Berndt SI, Mannetje A, de Roos AJ, Kricker A, Nieters A, Franceschi S, Melbye M, Boffetta P, Clavel J, Linet MS, Weisenburger DD, Slager SL
Source: J Natl Cancer Inst Monogr, 2014 Aug;2014(48), p. 1-14.
PMID: 25174022
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Copy number variation analysis on a non-Hodgkin lymphoma case-control study identifies an 11q25 duplication associated with diffuse large B-cell lymphoma.
Authors: Conde L, Riby J, Zhang J, Bracci PM, Skibola CF
Source: PLoS One, 2014;9(8), p. e105382.
EPub date: 2014 Aug 18.
PMID: 25133503
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Follicular lymphoma-protective HLA class II variants correlate with increased HLA-DQB1 protein expression.
Authors: Sillé FC, Conde L, Zhang J, Akers NK, Sanchez S, Maltbaek J, Riby JE, Smith MT, Skibola CF
Source: Genes Immun, 2014 Mar;15(2), p. 133-6.
EPub date: 2013 Dec 5.
PMID: 24304973
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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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X chromosome-wide association study of follicular lymphoma.
Authors: Conde L, Foo JN, Riby J, Liu J, Darabi H, Hjalgrim H, Bracci PM, Smedby KE, Skibola CF
Source: Br J Haematol, 2013 Sep;162(6), p. 858-62.
EPub date: 2013 Jun 25.
PMID: 23795672
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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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Rare variant association testing under low-coverage sequencing.
Authors: Navon O, Sul JH, Han B, Conde L, Bracci PM, Riby J, Skibola CF, Eskin E, Halperin E
Source: Genetics, 2013 Jul;194(3), p. 769-79.
EPub date: 2013 May 1.
PMID: 23636738
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