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Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes

  1. Author:
    Moore, Amy
    Machiela, Mitchell J
    Machado, Moara
    Wang, Sophia S
    Kane, Eleanor
    Slager, Susan L
    Zhou, Weiyin
    Carrington,Mary
    Lan, Qing
    Milne, Roger L
    Birmann, Brenda M
    Adami, Hans-Olov
    Albanes, Demetrius
    Arslan, Alan A
    Becker, Nikolaus
    Benavente, Yolanda
    Bisanzi, Simonetta
    Boffetta, Paolo
    Bracci, Paige M
    Brennan, Paul
    Brooks-Wilson, Angela R
    Canzian, Federico
    Caporaso, Neil
    Clavel, Jacqueline
    Cocco, Pierluigi
    Conde, Lucia
    Cox, David G
    Cozen, Wendy
    Curtin, Karen
    De Vivo, Immaculata
    de Sanjose, Silvia
    Foretova, Lenka
    Gapstur, Susan M
    Ghesquières, Hervè
    Giles, Graham G
    Glenn, Martha
    Glimelius, Bengt
    Gao, Chi
    Habermann, Thomas M
    Hjalgrim, Henrik
    Jackson, Rebecca D
    Liebow, Mark
    Link, Brian K
    Maynadie, Marc
    McKay, James
    Melbye, Mads
    Miligi, Lucia
    Molina, Thierry J
    Monnereau, Alain
    Nieters, Alexandra
    North, Kari E
    Offit, Kenneth
    Patel, Alpa V
    Piro, Sara
    Ravichandran, Vignesh
    Riboli, Elio
    Salles, Gilles
    Severson, Richard K
    Skibola, Christine F
    Smedby, Karin E
    Southey, Melissa C
    Spinelli, John J
    Staines, Anthony
    Stewart, Carolyn
    Teras, Lauren R
    Tinker, Lesley F
    Travis, Ruth C
    Vajdic, Claire M
    Vermeulen, Roel C H
    Vijai, Joseph
    Weiderpass, Elisabete
    Weinstein, Stephanie
    Doo, Nicole Wong
    Zhang, Yawei
    Zheng, Tongzhang
    Chanock, Stephen J
    Rothman, Nathaniel
    Cerhan, James R
    Dean,Michael
    Camp, Nicola J
    Yeager,Meredith
    Berndt, Sonja I

  2. Author Address

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA., Departamento de Biologia Geral, Instituto de Ci 234;ncias Biol 243;gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil., Division of Health Analytics, City of Hope Beckman Research Institute, Duarte, CA 91010, USA., Department of Health Sciences, University of York, York YO10 5DD, UK., Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA., Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD 20877, USA., Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD 20892, USA., Ragon Institute of MGH, Cambridge, MA 02139, USA., Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia., Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia., Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria 3800, Australia., Channing Division of Network Medicine, Department of Medicine, Brigham and Women 39;s Hospital and Harvard Medical School, Boston, MA 02115, USA., Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17176, Sweden., Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA., Institute of Health and Society, Clinical Effectiveness Research Group, University of Oslo, Oslo 0315, Norway., Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY 10016, USA., Department of Population Health, New York University School of Medicine, New York, NY 10016, USA., Perlmutter Comprehensive Cancer Center, NYU Langone Health, New York, NY 10016, USA., Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-W 252;rttemberg 69120, Germany., Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L 39;Hospitalet de Llobregat, Barcelona 08908, Spain., Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Barcelona 08036, Spain., Regional Cancer Prevention Laboratory, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence 50139, Italy., Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA., Department of Medical and Surgical Sciences, University of Bologna, Bologna 41026, Italy., Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94118, USA., International Agency for Research on Cancer (IARC), Lyon 69372, France., Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z1L3, Canada., Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia V5A1S6, Canada., Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany., Center of Research in Epidemiology and Statistics Sorbonne Paris Cit 233; (CRESS), UMR1153, INSERM, Villejuif 75004, France., Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari 09042, Italy., Bill Lyons Informatics Centre, UCL Cancer Institute, University College London, London WC1E 6DD, UK., INSERM U1052, Cancer Research Center of Lyon, Centre L 233;on B 233;rard, Lyon 69008, France., Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA., Department of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA., Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno 656 53, Czech Republic., Department of Population Science, American Cancer Society, Atlanta, GA 30303, USA., Department of Hematology, Centre L 233;on B 233;rard, Lyon 69008, France., INSERM U1052, Cancer Research Center of Lyon, Lyon-1 University, Pierre-B 233;nite Cedex 69008, France., Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75105, Sweden., Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA., Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark., Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH 43210, USA., Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA., U1231, Registre des H 233;mopathies Malignes de C 244;te d 39;Or, University of Burgundy and Dijon University Hospital, Dijon 21070, France., Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Environmental and Occupational Epidemiology Branch-Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence 50139, Italy., Department of Pathology, AP-HP, Necker Enfants Malades, Universit 233; Paris Descartes, EA 7324, Sorbonne Paris Cit 233; 75015, France., Registre des H 233;mopathies Malignes de la Gironde, Institut Bergoni 233;, Bordeaux Cedex 33076, France., Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-W 252;rttemberg 79108, Germany., Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., School of Public Health, Imperial College London, London W2 1PG, UK., Department of Hematology, Hospices Civils de Lyon, Pierre Benite Cedex 69495, France., Department of Hematology, Universit 233; Lyon-1, Pierre Benite Cedex 69495, France., Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI 48201, USA., Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA., Department of Medicine, Solna, Karolinska Institutet, Stockholm 17176, Sweden., Hematology Center, Karolinska University Hospital, Stockholm 17176, Sweden., Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia., Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia V5Z1L3, Canada., School of Population and Public Health, University of British Columbia, Vancouver, British Columbia V6T1Z3, Canada., School of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin 9, Ireland., Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98117, USA., Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK., Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales 2052, Australia., Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3584 CG, The Netherlands., Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, The Netherlands., Concord Clinical School, University of Sydney, Concord, New South Wales 2139, Australia., Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA., Department of Epidemiology, Brown University, Providence, RI 02903, USA.,
    1. Year: 2021
    2. Epub Date: 2021 06 17
  2. Journal: Journal of translational genetics and genomics
    1. 5
    2. Pages: 200-217
  4. Type of Article: Article
  1. Abstract:

    Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk. We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis. We discovered positive associations between FROH and CLL (ß = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (ß = 11.4, SE = 5.82, P = 0.02) but not DLBCL (P = 1.0) or MZL (P = 0.91). For F3, we observed an association with CLL (ß = 27.5, SE = 6.51, P = 2.4 × 10-5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.

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  2. DOI: 10.20517/jtgg.2021.08
  3. PMID: 34622145
  4. PMCID: PMC8494431

Library Notes

  1. Fiscal Year: FY2020-2021
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