ArticleJournal of translational genetics and genomics2021
Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.
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82 authors at 20 institutions in 13 countries.
Amy MooreDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Mitchell J MachielaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Moara MachadoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Sophia S WangDivision of Health Analytics, City of Hope Beckman Research Institute, Duarte, CA 91010, USA.
Eleanor KaneDepartment of Health Sciences, University of York, York YO10 5DD, UK.
Susan L SlagerDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Weiyin ZhouDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Mary CarringtonBasic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD 20892, USA.
Qing LanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Roger L MilneCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
Brenda M BirmannChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Hans-Olov AdamiDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17176, Sweden.
Demetrius AlbanesDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Alan A ArslanDepartment of Obstetrics and Gynecology, New York University School of Medicine, New York, NY 10016, USA.
Nikolaus BeckerDivision of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg 69120, Germany.
Yolanda BenaventeCancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
Simonetta BisanziRegional Cancer Prevention Laboratory, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence 50139, Italy.
Paolo BoffettaStony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA.
Paige M BracciDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94118, USA.
Paul BrennanInternational Agency for Research on Cancer (IARC), Lyon 69372, France.
Angela R Brooks-WilsonGenome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z1L3, Canada.
Federico CanzianGenomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Neil CaporasoDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Jacqueline ClavelCenter of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), UMR1153, INSERM, Villejuif 75004, France.
Pierluigi CoccoDepartment of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari 09042, Italy.
Lucia CondeBill Lyons Informatics Centre, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
David G CoxINSERM U1052, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon 69008, France.
Wendy CozenDepartment of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Karen CurtinDepartment of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Immaculata De VivoChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Silvia de SanjoseDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Lenka ForetovaDepartment of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno 656 53, Czech Republic.
Susan M GapsturDepartment of Population Science, American Cancer Society, Atlanta, GA 30303, USA.
Hervè GhesquièresDepartment of Hematology, Centre Léon Bérard, Lyon 69008, France.
Graham G GilesCancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
Martha GlennDepartment of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Bengt GlimeliusDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75105, Sweden.
Chi GaoDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Thomas M HabermannDepartment of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Henrik HjalgrimDepartment of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark.
Rebecca D JacksonDivision of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH 43210, USA.
Mark LiebowDepartment of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Brian K LinkDepartment of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Marc MaynadieU1231, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon 21070, France.
James McKayInternational Agency for Research on Cancer (IARC), Lyon 69372, France.
Mads MelbyeDepartment of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark.
Lucia MiligiEnvironmental and Occupational Epidemiology Branch-Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence 50139, Italy.
Thierry J MolinaDepartment of Pathology, AP-HP, Necker Enfants Malades, Université Paris Descartes, EA 7324, Sorbonne Paris Cité 75015, France.
Alain MonnereauCenter of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), UMR1153, INSERM, Villejuif 75004, France.
Alexandra NietersCenter for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg 79108, Germany.
Kari E NorthDepartment of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kenneth OffitDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Alpa V PatelDepartment of Population Science, American Cancer Society, Atlanta, GA 30303, USA.
Sara PiroEnvironmental and Occupational Epidemiology Branch-Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence 50139, Italy.
Vignesh RavichandranDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Elio RiboliSchool of Public Health, Imperial College London, London W2 1PG, UK.
Gilles SallesINSERM U1052, Cancer Research Center of Lyon, Lyon-1 University, Pierre-Bénite Cedex 69008, France.
Richard K SeversonDepartment of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Christine F SkibolaDepartment of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Karin E SmedbyDepartment of Medicine, Solna, Karolinska Institutet, Stockholm 17176, Sweden.
Melissa C SoutheyGenetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia.
John J SpinelliCancer Control Research, BC Cancer Agency, Vancouver, British Columbia V5Z1L3, Canada.
Anthony StainesSchool of Nursing, Psychotherapy and Community Health, Dublin City University, Dublin 9, Ireland.
Carolyn StewartDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Lauren R TerasDepartment of Population Science, American Cancer Society, Atlanta, GA 30303, USA.
Lesley F TinkerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98117, USA.
Ruth C TravisCancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK.
Claire M VajdicCentre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales 2052, Australia.
Roel C H VermeulenInstitute for Risk Assessment Sciences, Utrecht University, Utrecht 3584 CG, The Netherlands.
Joseph VijaiDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Elisabete WeiderpassInternational Agency for Research on Cancer (IARC), Lyon 69372, France.
Stephanie WeinsteinDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Nicole Wong DooConcord Clinical School, University of Sydney, Concord, New South Wales 2139, Australia.
Yawei ZhangDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA.
Tongzhang ZhengDepartment of Epidemiology, Brown University, Providence, RI 02903, USA.
Stephen J ChanockDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Nathaniel RothmanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
James R CerhanDepartment of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Michael DeanDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Nicola J CampDepartment of Internal Medicine and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Meredith YeagerDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Sonja I BerndtDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
National Cancer Institute · USDivision of Cancer Epidemiology and GeneticsMemorial Sloan Kettering Cancer Center · USAmerican Cancer Society · USCentre International de Recherche sur le Cancer · FRHarvard University · USCancer Council Victoria · AUGerman Cancer Research Center · DEMayo Clinic in Florida · USStatens Serum Institut · DKWinnMed · USBrown University · USDublin City University · IEEmory University · USFred Hutch Cancer Center · USImperial College London · GBKarolinska Institutet · SEKarolinska University Hospital · SELaboratoire d’immunologie intégrative du cancer · FRMasaryk Memorial Cancer Institute · CZ
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ANIRBAN MAITRA · 1985 to 2026
$83.1MStatistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ROSNER, BERNARD A · 2000 to 2019
$77.8MUTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI KATHARINE S ULLMAN · 1986 to 2026
$72.6MViral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0MThe Role of Monocytes in non-Hodgkin LymphomaP50CA097274 · NCI · UNIVERSITY OF IOWA · PI LENTZ, STEVEN R · 2002 to 2021
$45.7MMayo Clinic Center for Translational Science ActivitiesUL1TR000135 · NCATS · MAYO CLINIC ROCHESTER · PI KHOSLA, SUNDEEP · 2012 to 2015
$41.2MCancer Risk in Human PopulationsZIACP010136 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI PURDUE, MARK · 2009 to 2025
$36.7MRESEARCH IN ENVIRONMENTAL HEALTH SCIENCES (CENTER GRANT)P30ES000260 · NIEHS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ZELIKOFF, JUDITH TERRY · 1985 to 2020
$26.1MCALIFORNIA'S PARTICIPATION IN THE NATIONAL CANCER PREVENTION AND CONTRO PROGRAMU58DP000807 · DP · PUBLIC HEALTH INSTITUTE · PI SNIPES, KURT P · 2007 to 2011
$22.5MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MCCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA CP010136NCATS NIH HHS UL1 TR000135NCCDPHP CDC HHS U58 DP000807NCI NIH HHS HHSN261200800001ENCI NIH HHS HHSN261201000026CNCI NIH HHS HHSN261201000034CNCI NIH HHS HHSN261201000035CNCI NIH HHS HHSN261201000035INCI NIH HHS HHSN261201000140CNCI NIH HHS K08 CA134919NCI NIH HHS N01 CO012400NCI NIH HHS N01 PC065064NCI NIH HHS N01 PC067008NCI NIH HHS N01 PC067009NCI NIH HHS N01 PC067010NCI NIH HHS P01 CA087969NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA016087NCI NIH HHS P30 CA042014NCI NIH HHS P30 CA086862NCI NIH HHS P50 CA097274NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA062006NCI NIH HHS R01 CA092153NCI NIH HHS R01 CA098122NCI NIH HHS R01 CA098661NCI NIH HHS R01 CA134674NCI NIH HHS R01 CA134958NCI NIH HHS R01 CA148690NCI NIH HHS R01 CA149445NCI NIH HHS R01 CA154643NCI NIH HHS R01 CA200703NCI NIH HHS R21 CA165923NCI NIH HHS U01 CA049449NCI NIH HHS U01 CA118444NCI NIH HHS U01 CA167552NCI NIH HHS UM1 CA186107NHGRI NIH HHS U01 HG007033NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS HHSN268201100002INHLBI NIH HHS HHSN268201100003INHLBI NIH HHS HHSN268201100004INHLBI NIH HHS HHSN268201100046CNIA NIH HHS HHSN271201100004CNIEHS NIH HHS P30 ES000260WHI NIH HHS HHSN268201100001CWHI NIH HHS HHSN268201100002CWHI NIH HHS HHSN268201100003CWHI NIH HHS HHSN268201100004CWorld Health Organization 001
Abstract
aimRecessive 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.
methodsWe 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.
resultsWe discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41,
conclusionOur 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.
Indexed as
chronic lymphocytic leukemiadiffuse large B-cell lymphomafollicular lymphomahomozygositymarginal zone lymphomaNon-Hodgkin lymphoma
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