Journal article
HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
Cancer research (Chicago, Ill.), Vol.78(14), pp.4086-4096
07/15/2018
DOI: 10.1158/0008-5472.CAN-17-2900
PMCID: PMC6065509
PMID: 29735552
Abstract
A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (
trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.
HLA gene diversity reduces risk for non-Hodgkin lymphoma.
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Details
- Title: Subtitle
- HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
- Creators
- Sophia S Wang - Department of Population Sciences, Beckman Research Institute and the City of Hope, Duarte, California. sowang@coh.orgMary Carrington - Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, and Ragon Institute of MGH, MIT, and Harvard, Cambridge, MassachusettsSonja I Berndt - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandSusan L Slager - Department of Health Sciences Research, Mayo Clinic, Rochester, MinnesotaPaige M Bracci - Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CaliforniaJenna Voutsinas - Department of Population Sciences, Beckman Research Institute and the City of Hope, Duarte, CaliforniaJames R Cerhan - Department of Health Sciences Research, Mayo Clinic, Rochester, MinnesotaKarin E Smedby - Hematology Center, Karolinska University Hospital, Stockholm, SwedenHenrik Hjalgrim - Department of Hematology, Rishospitalet, Copenhagen, DenmarkJoseph Vijai - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New YorkLindsay M Morton - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandRoel Vermeulen - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the NetherlandsOra Paltiel - Braun School of Public Health and Community Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, IsraelClaire M Vajdic - Centre for Big Data Research in Health, The University of New South Wales, Sydney, New South Wales, AustraliaMartha S Linet - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandAlexandra Nieters - Centre for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg, GermanySilvia de Sanjose - CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, SpainWendy Cozen - Norris Comprehensive Cancer Center, Keck School of Medicine of USC, Departments of Preventive Medicine and Pathology, University of Southern California, Los Angeles, CalforniaElizabeth E Brown - Department of Pathology, School of Medicine and the UAB Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AlabamaJennifer Turner - Faculty of Medicine and Health Sciences, Macquarie University, Sydney, AustraliaJohn J Spinelli - School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, CanadaTongzhang Zheng - Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode IslandBrenda M Birmann - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MassachusettsChristopher R Flowers - Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GeorgiaNikolaus Becker - Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Baden-Württemberg, GermanyElizabeth A Holly - Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CaliforniaEleanor Kane - Department of Health Sciences, University of York, York, United KingdomDennis Weisenburger - Department of Pathology, City of Hope, Duarte, CaliforniaMarc Maynadie - Registry of Hematological Malignancies of Cote d'Or, INSERM UMR1231, University of Burgundy and Dijon University Hospital, Dijon, FrancePierluigi Cocco - Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, ItalyDemetrius Albanes - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandStephanie J Weinstein - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandLauren R Teras - Epidemiology Research Program, American Cancer Society, Atlanta, GeorgiaW Ryan Diver - Epidemiology Research Program, American Cancer Society, Atlanta, GeorgiaStephanie J Lax - Department of Health Sciences, University of York, York, United KingdomRuth C Travis - Cancer Epidemiology Unit, University of Oxford, Oxford, United KingdomRudolph Kaaks - Division of Clinical Epidemiology, German Cancer Research Centre, Heidelberg, Baden-Württemberg, GermanyElio Riboli - School of Public Health, Imperial College London, London, United KingdomYolanda Benavente - CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, SpainPaul Brennan - International Agency for Research on Cancer, Lyon, FranceJames McKay - Department of Immunology, CHU Henri Mondor, Créteil, FranceMarie-Hélène Delfau-Larue - INSERM U 955, CHU Henri Mondor, Créteil, FranceBrian K Link - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IowaCorrado Magnani - Center of Oncological Prevention (CPO) Piemonte and Unit of Medical Statistics and Epidemiology, Department Translational Medicine, University of Piemonte Orientale, Novara, ItalyMaria Grazia Ennas - Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari, ItalyGiancarlo Latte - Division of Hematology, S. Francesco Hospital, Nuoro, ItalyAndrew L Feldman - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MinnesotaNicole Wong Doo - Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, AustraliaGraham G Giles - Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, AustraliaMelissa C Southey - Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Victoria, AustraliaRoger L Milne - Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, AustraliaKenneth Offit - Department of Hematology, Rishospitalet, Copenhagen, DenmarkJacob Musinsky - Department of Hematology, Rishospitalet, Copenhagen, DenmarkAlan A Arslan - Perlmutter Cancer Center, NYU Langone Medical Center, New York City, New YorkMark P Purdue - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandHans-Olov Adami - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenMads Melbye - Department of Medicine, Stanford University School of Medicine, Stanford, CalforniaBengt Glimelius - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenLucia Conde - Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, United KingdomNicola J Camp - Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UtahMartha Glenn - Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UtahKaren Curtin - Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UtahJacqueline Clavel - Université Paris Descartes, Paris, FranceAlain Monnereau - Registre des hémopathies malignes de la Gironde, Institut Bergonié, University of Bordeaux, Inserm, Team EPICENE, UMR 1219, FranceDavid G Cox - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Cancer Research Center of Lyon, INSERM UMR1052, Center Léon Bérard, Lyon, FranceHervé Ghesquières - Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex, FranceGilles Salles - Department of Hematology, Hospices Civils De Lyon, Centre Hospitalier Lyon-Sud and Université Claude Bernard, Lyon, FrancePaulo Bofetta - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New YorkLenka Foretova - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, MF MU, Brno, Czech RepublicAnthony Staines - School of Nursing and Human Sciences, Dublin City University, Dublin, IrelandScott Davis - Fred Hutchinson Cancer Research Center and School of Public Health and Community Medicine, University of Washington, Seattle, WashingtonRichard K Severson - Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MichiganQing Lan - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandAngela Brooks-Wilson - Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, CanadaMartyn T Smith - Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CaliforniaEve Roman - Department of Health Sciences, University of York, York, United KingdomAnne Kricker - Sydney School of Public Health, The University of Sydney, Sydney, AustraliaYawei Zhang - Department of Environmental Health Sciences, Yale School of Public Health, New HavenPeter Kraft - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MassachusettsStephen J Chanock - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandNathaniel Rothman - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandPatricia Hartge - Division of Cancer Epidemiology and Genetics, NCI, Bethesda, MarylandChristine F Skibola - Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.78(14), pp.4086-4096
- Publisher
- United States
- DOI
- 10.1158/0008-5472.CAN-17-2900
- PMID
- 29735552
- PMCID
- PMC6065509
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Grant note
- R01 CA092153 / NCI NIH HHS U58 DP000807 / NCCDPHP CDC HHS R01 CA154643 / NCI NIH HHS R01 CA200703 / NCI NIH HHS U01 HG007033 / NHGRI NIH HHS P30 CA033572 / NCI NIH HHS R01 CA062006 / NCI NIH HHS N01 PC067008 / NCI NIH HHS N01 PC065064 / NCI NIH HHS P30 CA015083 / NCI NIH HHS P50 CA097274 / NCI NIH HHS U01 CA049449 / NCI NIH HHS R01 CA098122 / NCI NIH HHS HHSN261201000035C / NCI NIH HHS HHSN261201000140C / NCI NIH HHS N01CO12400 / NCI NIH HHS R01 CA148690 / NCI NIH HHS HHSN261201500005C / NCI NIH HHS U01 CA167552 / NCI NIH HHS UM1 CA167552 / NCI NIH HHS R01 CA098661 / NCI NIH HHS N01 PC067010 / NCI NIH HHS P30 ES000260 / NIEHS NIH HHS R03 CA179558 / NCI NIH HHS CIHR UL1 TR000135 / NCATS NIH HHS HHSN261200800001C / CCR NIH HHS HHSN261201000034C / NCI NIH HHS P01 CA087969 / NCI NIH HHS P30 CA008748 / NCI NIH HHS K08 CA134919 / NCI NIH HHS P30 CA086862 / NCI NIH HHS UM1 CA186107 / NCI NIH HHS R01 CA149445 / NCI NIH HHS Cancer Research UK R01 CA134674 / NCI NIH HHS P30 CA042014 / NCI NIH HHS R01 CA049449 / NCI NIH HHS U01 CA118444 / NCI NIH HHS R21 CA165923 / NCI NIH HHS HHSN261201000026C / NCI NIH HHS P30 CA016087 / NCI NIH HHS N01 PC067009 / NCI NIH HHS HHSN261201000035I / NCI NIH HHS HHSN261200800001E / NCI NIH HHS
- Language
- English
- Date published
- 07/15/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984071698502771
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