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Grant Details

Grant Number: 5R01CA149445-03 Interpret this number
Primary Investigator: Birmann, Brenda
Organization: Brigham And Women'S Hosp., Inc.
Project Title: A Prospective Analysis of Peripheral Blood Cytokines and Non-Hodgkin Lymphoma
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by applicant): Non-Hodgkin lymphoma (NHL) comprises a heterogeneous group of >30 lymphoid neoplasms, >85% of which are of B cell lineage. NHL presents a considerable public health burden with >80,500 new diagnoses and 24,600 deaths expected in 2010. The etiology of NHL is poorly understood, but it is known that overt immune compromise is a strong risk factor. Immune dysregulation may also be important in the etiology of NHL in persons with no overt immune deficiency. The Epstein-Barr virus (EBV) is detected in a sizeable minority of NHL in immune competent persons, but neither the true prevalence nor risk factors for EBV+ NHL are known. Th17, Th1, and Th2 cytokines mediate human immune responses and may be associated with NHL risk by virtue of their roles in B and T lymphocyte activation and inflammation. The Th17 response leads to the induction of several B cell stimulatory cytokines; this axis is also implicated in autoimmune disease, and persons with autoimmune conditions have an increased risk of NHL. It is plausible that Th17 dysregulation, and/or dysregulation of Th1 or Th2 or inflammatory responses, is associated with NHL risk in apparently immune competent adults. Cytokines also mediate host control of EBV and thus may also predict risk of EBV+ NHL. To examine these hypotheses, we will conduct prospective studies nested within the Nurses' Health Study and Health Professionals Follow-up Study cohorts. In a projected pooled sample of 670 cases and 1340 matched controls, we will measure a panel of immune markers in pre-diagnostic plasma samples. We will collect tissue specimens from NHL cases for pathologic studies to determine WHO-defined histologic subtype, diffuse large B-cell lymphoma (DLBCL) molecular subtype, and EBV status. We will use conditional logistic regression to assess the association of plasma immune markers indicative of altered Th17, Th1, Th2 and/or inflammatory responses with NHL. We will evaluate confounding by other NHL risk factors and conduct secondary analyses to examine effect modification and explore the correlation of plasma immune markers with those other factors. With these studies we will be the first to examine the etiologic role of the Th17 response in NHL, to report population-based prevalences of EBV+ NHL by subtype and of DLBCL subtypes, and to prospectively evaluate risk factors for EBV+ NHL. The multidisciplinary study team features epidemiologists (Drs. Birmann, Laden, and Giovannucci), a senior biostatistician (Dr. Rosner), and immunologists (Drs. Martmnez-Maza and Breen) and hematopathologists (Drs. Aster and Rodig) with substantial relevant experience-i.e, in the use of plasma immune markers in etiologic studies, prospective data analysis, and the pathologic determination of NHL histologic type and tumor EBV status. With this highly qualified team, the extraordinary resources of the cohorts, and the proposed studies, we are uniquely situated to contribute novel insights on the role of immune dysregulation in the etiology of NHL and EBV+ NHL in immunocompetent adults.

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Publications

Regular aspirin use and risk of multiple myeloma: a prospective analysis in the health professionals follow-up study and nurses' health study.
Authors: Birmann BM, Giovannucci EL, Rosner BA, Colditz GA
Source: Cancer Prev Res (Phila), 2014 Jan;7(1), p. 33-41.
EPub date: 2013 Nov 26.
PMID: 24282256
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Temporal stability of serum concentrations of cytokines and soluble receptors measured across two years in low-risk HIV-seronegative men.
Authors: Epstein MM, Breen EC, Magpantay L, Detels R, Lepone L, Penugonda S, Bream JH, Jacobson LP, Martínez-Maza O, Birmann BM
Source: Cancer Epidemiol Biomarkers Prev, 2013 Nov;22(11), p. 2009-15.
EPub date: 2013 Aug 27.
PMID: 23983237
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A pooled analysis of alcohol consumption and risk of multiple myeloma in the international multiple myeloma consortium.
Authors: Andreotti G, Birmann B, De Roos AJ, Spinelli J, Cozen W, Camp NJ, Moysich K, Chiu B, Steplowski E, Krzystan J, Boffetta P, Benhaim-Luzon V, Brennan P, de Sanjosé S, Costas L, Costantini AS, Miligi L, Cocco P, Becker N, Foretová L, Maynadié M, Nieters A, Staines A, Tricot G, Milliken K, Weisenburger D, Zheng T, Baris D, Purdue MP
Source: Cancer Epidemiol Biomarkers Prev, 2013 Sep;22(9), p. 1620-7.
EPub date: 2013 Aug 20.
PMID: 23964064
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A prospective analysis of body size during childhood, adolescence, and adulthood and risk of non-Hodgkin lymphoma.
Authors: Bertrand KA, Giovannucci E, Zhang SM, Laden F, Rosner B, Birmann BM
Source: Cancer Prev Res (Phila), 2013 Aug;6(8), p. 864-73.
EPub date: 2013 Jun 26.
PMID: 23803416
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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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