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

About this Publication
Title
Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes.
Pubmed ID
34622145 (View this publication on the PubMed website)
Digital Object Identifier
Publication
J Transl Genet Genom. 2021; Volume 5: Pages 200-217
Authors
Moore A, Machiela MJ, Machado M, Wang SS, Kane E, Slager SL, Zhou W, Carrington M, Lan Q, Milne RL, Birmann BM, Adami HO, Albanes D, Arslan AA, Becker N, Benavente Y, Bisanzi S, Boffetta P, Bracci PM, Brennan P, ...show more Brooks-Wilson AR, Canzian F, Caporaso N, Clavel J, Cocco P, Conde L, Cox DG, Cozen W, Curtin K, De Vivo I, de Sanjose S, Foretova L, Gapstur SM, Ghesquières H, Giles GG, Glenn M, Glimelius B, Gao C, Habermann TM, Hjalgrim H, Jackson RD, Liebow M, Link BK, Maynadie M, McKay J, Melbye M, Miligi L, Molina TJ, Monnereau A, Nieters A, North KE, Offit K, Patel AV, Piro S, Ravichandran V, Riboli E, Salles G, Severson RK, Skibola CF, Smedby KE, Southey MC, Spinelli JJ, Staines A, Stewart C, Teras LR, Tinker LF, Travis RC, Vajdic CM, Vermeulen RCH, Vijai J, Weiderpass E, Weinstein S, Doo NW, Zhang Y, Zheng T, Chanock SJ, Rothman N, Cerhan JR, Dean M, Camp NJ, Yeager M, Berndt SI
Affiliations
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
  • 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.
  • Basic Science Program, Frederick National Laboratory for Cancer Research in the Laboratory of Integrative Cancer Immunology, National Cancer Institute, Bethesda, MD 20892, USA.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17176, Sweden.
  • Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY 10016, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg 69120, Germany.
...show more
  • Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, 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 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.
  • Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
  • Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (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 Léon Bérard, Lyon 69008, France.
  • Department of Preventive Medicine, 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 Léon Bérard, Lyon 69008, France.
  • Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 75105, Sweden.
  • Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
  • 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 Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon 21070, France.
  • 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, Université Paris Descartes, EA 7324, Sorbonne Paris Cité 75015, France.
  • Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg 79108, Germany.
  • Department of Epidemiology, 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.
  • INSERM U1052, Cancer Research Center of Lyon, Lyon-1 University, Pierre-Bénite Cedex 69008, 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.
  • 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 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.
  • 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.
Abstract

AIM: 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.

METHODS: 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.

RESULTS: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, P = 1.6 × 10-6) and FL (β = 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 (β = 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.

CONCLUSION: 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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