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Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.

About this Publication
Title
Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.
Pubmed ID
36273105 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Leukemia. 2022 Dec; Volume 36 (Issue 12): Pages 2835-2844
Authors
Berndt SI, Vijai J, Benavente Y, Camp NJ, Nieters A, Wang Z, Smedby KE, Kleinstern G, Hjalgrim H, Besson C, Skibola CF, Morton LM, Brooks-Wilson AR, Teras LR, Breeze C, Arias J, Adami HO, Albanes D, Anderson KC, Ansell SM, ...show more Bassig B, Becker N, Bhatti P, Birmann BM, Boffetta P, Bracci PM, Brennan P, Brown EE, Burdett L, Cannon-Albright LA, Chang ET, Chiu BCH, Chung CC, Clavel J, Cocco P, Colditz G, Conde L, Conti DV, Cox DG, Curtin K, Casabonne D, De Vivo I, Diepstra A, Diver WR, Dogan A, Edlund CK, Foretova L, Fraumeni JF, Gabbas A, Ghesquières H, Giles GG, Glaser S, Glenn M, Glimelius B, Gu J, Habermann TM, Haiman CA, Haioun C, Hofmann JN, Holford TR, Holly EA, Hutchinson A, Izhar A, Jackson RD, Jarrett RF, Kaaks R, Kane E, Kolonel LN, Kong Y, Kraft P, Kricker A, Lake A, Lan Q, Lawrence C, Li D, Liebow M, Link BK, Magnani C, Maynadie M, McKay J, Melbye M, Miligi L, Milne RL, Molina TJ, Monnereau A, Montalvan R, North KE, Novak AJ, Onel K, Purdue MP, Rand KA, Riboli E, Riby J, Roman E, Salles G, Sborov DW, Severson RK, Shanafelt TD, Smith MT, Smith A, Song KW, Song L, Southey MC, Spinelli JJ, Staines A, Stephens D, Sutherland HJ, Tkachuk K, Thompson CA, Tilly H, Tinker LF, Travis RC, Turner J, Vachon CM, Vajdic CM, Van Den Berg A, Van Den Berg DJ, Vermeulen RCH, Vineis P, Wang SS, Weiderpass E, Weiner GJ, Weinstein S, Doo NW, Ye Y, Yeager M, Yu K, Zeleniuch-Jacquotte A, Zhang Y, Zheng T, Ziv E, Sampson J, Chatterjee N, Offit K, Cozen W, Wu X, Cerhan JR, Chanock SJ, Slager SL, Rothman N
Affiliations
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md, USA. berndts@mail.nih.gov.
  • Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Department of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Institute for Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany.
  • Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
  • School of Public Health, University of Haifa, Haifa, Israel.
  • Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
  • Centre Hospitalier de Versailles, Le Chesnay, France.
...show more
  • Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md, USA.
  • Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
  • Department of Population Science, American Cancer Society, Atlanta, GA, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York, 11794, NY, USA.
  • Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
  • International Agency for Research on Cancer (IARC), Lyon, France.
  • Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MA, USA.
  • Department of Public Health Sciences University of Chicago, Chicago, IL, USA.
  • CRESS, UMR1153, INSERM, Villejuif, France.
  • Centre for Occupational and Environmental Health, Division of Population Science, Health Services Research & Primary Care, University of Manchester, Manchester, United Kingdom.
  • Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
  • Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London, United Kingdom.
  • Department of Population and Public Health Sciences, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • INSERM U1052, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon, France.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Departments of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
  • Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari, Italy.
  • Department of Hematology, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre Benite, France.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VC, Australia.
  • Cancer Prevention Institute of California, Fremont, CA, USA.
  • Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
  • Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA.
  • Lymphoid Malignancies Unit, Henri Mondor Hospital and University Paris Est, Créteil, France.
  • Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
  • Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH, USA.
  • MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
  • Department of Health Sciences, University of York, York, United Kingdom.
  • Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Information Systems and Decision Sciences, California State University, Fullerton, Fullerton, CA, USA.
  • Sydney School of Public Health, The University of Sydney, Sydney, NSW, Australia.
  • Westat, Rockville, MA, USA.
  • F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
  • CPO-Piemonte and Unit of Medical Statistics and Epidemiology, Department Translational Medicine, University of Piemonte Orientale, Novara, Italy.
  • INSERM U1231, EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, France.
  • Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, Italy.
  • Department of Pathology, APHP, Necker and Robert Debré, Université Paris Cité, Institut Imagine, INSERM U1163, Paris, France.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Donald and Barbara Zucker School of Medicine, Hofstra/Northwell, Hempstead, New York, NY, USA.
  • School of Public Health, Imperial College London, London, United Kingdom.
  • Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI, USA.
  • Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA, USA.
  • Leukemia/Bone Marrow Transplantation Program, BC Cancer Agency, Vancouver, BC, Canada.
  • Center for Cancer Research, National Cancer Institute, Frederick, MA, USA.
  • Cancer Control Research, BC Cancer Agency, Vancouver, BC, Canada.
  • School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin, Ireland.
  • Centre Henri Becquerel, Université de Rouen, Rouen, France.
  • Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
  • Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
  • Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
  • The Kirby Institute, University of New South Wales, Sydney, NSW, Australia.
  • Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
  • MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom.
  • Division of Health Analytics, City of Hope Beckman Research Institute, Duarte, CA, USA.
  • Concord Clinical School, University of Sydney, Concord, NSW, Australia.
  • Department of Population Health, New York University School of Medicine, New York, NY, USA.
  • Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
  • Department of Epidemiology, Brown University, Providence, RI, USA.
  • Division of General Internal Medicine, Department of Medicine, Institute of Human Genetics, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA, USA.
  • Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Abstract

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

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