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Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.

About this Publication
Title
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia.
Pubmed ID
26956414 (View this publication on the PubMed website)
Publication
Nat Commun. 2016 Mar; Volume 7: Pages 10933
Authors
Berndt SI, Camp NJ, Skibola CF, Vijai J, Wang Z, Gu J, Nieters A, Kelly RS, Smedby KE, Monnereau A, Cozen W, Cox A, Wang SS, Lan Q, Teras LR, Machado M, Yeager M, Brooks-Wilson AR, Hartge P, Purdue MP, ...show more Birmann BM, Vajdic CM, Cocco P, Zhang Y, Giles GG, Zeleniuch-Jacquotte A, Lawrence C, Montalvan R, Burdett L, Hutchinson A, Ye Y, Call TG, Shanafelt TD, Novak AJ, Kay NE, Liebow M, Cunningham JM, Allmer C, Hjalgrim H, Adami HO, Melbye M, Glimelius B, Chang ET, Glenn M, Curtin K, Cannon-Albright LA, Diver WR, Link BK, Weiner GJ, Conde L, Bracci PM, Riby J, Arnett DK, Zhi D, Leach JM, Holly EA, Jackson RD, Tinker LF, Benavente Y, Sala N, Casabonne D, Becker N, Boffetta P, Brennan P, Foretova L, Maynadie M, McKay J, Staines A, Chaffee KG, Achenbach SJ, Vachon CM, Goldin LR, Strom SS, Leis JF, Weinberg JB, Caporaso NE, Norman AD, De Roos AJ, Morton LM, Severson RK, Riboli E, Vineis P, Kaaks R, Masala G, Weiderpass E, Chirlaque MD, Vermeulen RCH, Travis RC, Southey MC, Milne RL, Albanes D, Virtamo J, Weinstein S, Clavel J, Zheng T, Holford TR, Villano DJ, Maria A, Spinelli JJ, Gascoyne RD, Connors JM, Bertrand KA, Giovannucci E, Kraft P, Kricker A, Turner J, Ennas MG, Ferri GM, Miligi L, Liang L, Ma B, Huang J, Crouch S, Park JH, Chatterjee N, North KE, Snowden JA, Wright J, Fraumeni JF, Offit K, Wu X, de Sanjose S, Cerhan JR, Chanock SJ, Rothman N, Slager SL
Affiliations
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
  • Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, Huntsman Cancer Institute and University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
  • Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA.
  • Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA.
  • Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
  • Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, 79108 Baden-Württemberg, Germany.
  • Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
  • Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm 17176, Sweden.
  • Epidemiology of Childhood and Adolescent Cancers Group, INSERM, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), F-94807 Paris, France.
...show more
  • Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
  • Department of Oncology, University of Sheffield, Sheffield, South Yorkshire S10 1NS, UK.
  • Division of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, California 91030, USA.
  • Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
  • Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z1L3.
  • Ontario Health Study, Toronto, Ontario, Canada M5G 0A3.
  • Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
  • Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, 09042 Cagliari, Italy.
  • Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut 06520, USA.
  • Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
  • Department of Population Health, New York University School of Medicine, New York, New York 10016, USA.
  • Westat, Rockville, Maryland 20850, USA.
  • Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, 2300 Copenhagen, Denmark.
  • Department of Immunology, Genetics and Pathology, Uppsala University, 75105 Uppsala, Sweden.
  • Center for Epidemiology and Computational Biology, Health Sciences, Exponent, Inc., Menlo Park, California 94025, USA.
  • Department of Internal Medicine, Huntsman Cancer Institute, Salt Lake City, Utah 84112, USA.
  • Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA.
  • Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
  • Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California 94118, USA.
  • Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 35233, USA.
  • Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio 43210, USA.
  • Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98117, USA.
  • Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
  • Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
  • Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, 08908L'Hospitalet de Llobregat, 08908 Barcelona, Spain.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, 69120 Baden-Württemberg, Germany.
  • The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • International Agency for Research on Cancer (IARC), 69372 Lyon, France.
  • Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, 656 53 Brno, Czech Republic.
  • EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, 21070 Dijon, France.
  • School of Nursing and Human Sciences, Dublin City University, Dublin 9, Ireland.
  • Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona 85054, USA.
  • Department of Medicine, Duke University and VA Medical Centers, Durham, North Carolina 27710, USA.
  • Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan 48201, USA.
  • School of Public Health, Imperial College London, London W2 1PG, UK.
  • MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
  • Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), 50139 Florence, Italy.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17177 Stockholm, Sweden.
  • CIBER de Epidemiología y Salud Pública (CIBERESP), 08036 Barcelona, Spain.
  • Institute for Risk Assessment Sciences, Utrecht University, Utrecht, 3508, TD, The Netherlands.
  • Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK.
  • Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia.
  • Chronic Disease Prevention Unit, National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
  • Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut 06520, USA.
  • Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z1L3.
  • Center for Lymphoid Cancer, BC Cancer Agency, Vancouver, British Columbia, Canada V5Z1L3.
  • Sydney School of Public Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
  • Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales 2109, Australia.
  • Department of Biomedical Science, University of Cagliari, Monserrato, 09042 Cagliari, Italy.
  • Interdisciplinary Department of Medicine, University of Bari, 70124 Bari, Italy.
  • Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), 50139 Florence, Italy.
  • Department of Health Sciences, University of York, York YO10 5DD, UK.
  • Department of Statistics, Dongguk University, Seoul 100-715, Republic of Korea.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Abstract

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

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