Journal article
Genome-wide Association Study Identifies Multiple Risk Loci for Chronic Lymphocytic Leukemia
Nature genetics, Vol.45(8), pp.868-876
08/2013
DOI: 10.1038/ng.2652
PMCID: PMC3729927
PMID: 23770605
Abstract
Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10−14), 18q21.33 (BCL2, P = 7.76 × 10−11), 11p15.5 (C11orf21, P = 2.15 × 10−10), 4q25 (LEF1, P = 4.24 × 10−10), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 × 10−9), 9p21.3 (CDKN2B-AS1, P = 1.27 × 10−8), 18q21.32 (PMAIP1, P = 2.51 × 10−8), 15q15.1 (BMF, P = 2.71 × 10−10) and 2p22.2 (QPCT, P = 1.68 × 10−8), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 × 10−18). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 × 10−8) and 5p15.33 (TERT, P = 1.92 × 10−7). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
Details
- Title: Subtitle
- Genome-wide Association Study Identifies Multiple Risk Loci for Chronic Lymphocytic Leukemia
- Creators
- Sonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USABrian K Link - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USAChristine F Skibola - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USAGeorge J Weiner - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USADavid Martin - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic of Barcelona, University of Barcelona, Barcelona, SpainVijai Joseph - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USANicola J Camp - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USAJames R Cerhan - Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USAAlexandra Nieters - Center of Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Hesse, GermanyZhaoming Wang - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAWendy Cozen - Department of Preventive Medicine, USC Keck School of Medicine, University of Southern California, Los Angeles, California, USAAlain Monnereau - U1018 EQ6, Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif Cedex, FranceSophia S Wang - Division of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, California, USARachel S Kelly - MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, United KingdomQing Lan - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USALauren R Teras - Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USANilanjan Chatterjee - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAPatricia Hartge - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USABrenda M Birmann - Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USACharles C Chung - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAMeredith Yeager - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAMark P Purdue - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAAngela R Brooks-Wilson - Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, CanadaBruce K Armstrong - Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, AustraliaPierluigi Cocco - Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari, ItalyYawei Zhang - Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USAGianluca Severi - Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, AustraliaAnne Zeleniuch-Jacquotte - Department of Population Health, New York University School of Medicine, New York, New York, USACharles Lawrence - Health Studies Sector, Westat, Rockville, Maryland, USALaurie Burdette - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAJeffrey Yuenger - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAAmy Hutchinson - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAKevin B Jacobs - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USATimothy G Call - Division of Hematology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USATait D Shanafelt - Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USAAnne J Novak - Department of Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USANeil E Kay - Division of Hematology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USAMark Liebow - Division of General Internal Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota, USAAlice H Wang - Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USAKarin E Smedby - Department of Medicine Solna, Karolinska Institutet, Stockholm, SwedenHans-Olov Adami - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenMads Melbye - Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, DenmarkBengt Glimelius - Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, SwedenEllen T Chang - Center for Epidemiology and Computational Biology, Health Sciences, Exponent, Inc., Menlo Park, California, USAMartha Glenn - Department of Internal Medicine, Huntsman Cancer Institute, Salt Lake City, Utah, USAKaren Curtin - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USALisa A Cannon-Albright - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USABrandt Jones - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USAW. Ryan Diver - Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USALucia Conde - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USAPaige M Bracci - Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USAJacques Riby - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USAElizabeth A Holly - Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California, USAMartyn T Smith - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, California, USARebecca D Jackson - Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio, USALesley F Tinker - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USAYolanda Benavente - Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d’Oncologia, IDIBELL, Barcelona, SpainNikolaus Becker - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, GermanyPaolo Boffetta - The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USALenka Foretova - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech RepublicPaul Brennan - Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer, Lyon, FranceMarc Maynadie - EA 4184, Registre des Hémopathies Malignes de Côte d’Or, University of Burgundy and Dijon University Hospital, Dijon, FranceJames McKay - Genetic Cancer susceptibility Group, Section of Genetics, International Agency for Research on Cancer, Lyon, FranceAnthony Staines - School of Nursing and Human Sciences, Dublin City University, Dublin, Leinster, IrelandKari G Rabe - Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USASara J Achenbach - Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USACeline M Vachon - Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USALynn R Goldin - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USASara S Strom - Department of Epidemiology, M.D. Anderson Cancer Center, Houston, Texas, USAMark C Lanasa - Department of Medicine, Duke University and VA Medical Centers, Durham, North Carolina, USALogan G Spector - Division of Epidemiology/Clinical Research, University of Minnesota, Minneapolis, Minnesota, USAJose F Leis - Division of Hematology/Oncology, College of Medicine, Mayo Clinic, Phoenix, Arizona, USAJulie M Cunningham - Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, Minnesota, USAJ. Brice Weinberg - Department of Medicine, Duke University and VA Medical Centers, Durham, North Carolina, USAVicki A Morrison - Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota, USANeil E Caporaso - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAAaron D Norman - Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USAMartha S Linet - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAAnneclaire J De Roos - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USALindsay M Morton - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USARichard K Severson - Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan, USAElio Riboli - School of Public Health, Imperial College London, London, United KingdomPaolo Vineis - MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, United KingdomRudolph Kaaks - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, GermanyDimitrios Trichopoulos - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USAGiovanna Masala - Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, ItalyElisabete Weiderpass - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, SwedenMaría-Dolores Chirlaque - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona, SpainRoel C H Vermeulen - Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The NetherlandsRuth C Travis - Cancer Epidemiology Unit, University of Oxford, Oxford, United KingdomGraham G Giles - Cancer Epidemiology Centre, Cancer Council Victoria, Carlton, Victoria, AustraliaDemetrius Albanes - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAJarmo Virtamo - Department of Chronic Disease and Prevention, National Institute for Health and Welfare, Helsinki, FinlandStephanie Weinstein - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USAJacqueline Clavel - U1018 EQ6, Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif Cedex, FranceTongzhang Zheng - Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USATheodore R Holford - Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USAKenneth Offit - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USAAndrew Zelenetz - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USARobert J Klein - Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USAJohn J Spinelli - Cancer Control Research, BC Cancer Agency, Vancouver, British Columbia, CanadaKimberly A Bertrand - Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USAFrancine Laden - Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USAEdward Giovannucci - Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USAPeter Kraft - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USAAnne Kricker - Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, AustraliaJenny Turner - Pathology, Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, AustraliaClaire M Vajdic - Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, AustraliaMaria Grazia Ennas - Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari, ItalyGiovanni M Ferri - Interdisciplinary Department of Medicine, University of Bari, Bari, ItalyLucia Miligi - Environmental and Occupational Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Florence, ItalyLiming Liang - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USAJoshua Sampson - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USASimon Crouch - Epidemiology and Genetics Unit, Department of Health Sciences, University of York, York, United KingdomJu-hyun Park - Dongguk University-Seoul, Seoul, South KoreaKari E North - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USAAngela Cox - Department of Oncology, University of Sheffield, Sheffield, UKJohn A Snowden - Department of Oncology, University of Sheffield and Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UKJosh Wright - Department of Oncology, University of Sheffield and Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UKAngel Carracedo - Genomic Medicine Group CIBERER, University of Santiago de Compostela, Santiago de Compostela, SpainCarlos Lopez-Otin - Department of Biochemistry and Molecular Biology, Institute of Oncology, University of Oviedo, Oviedo, SpainSilvia Bea - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic of Barcelona, University of Barcelona, Barcelona, SpainItziar Salaverria - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic of Barcelona, University of Barcelona, Barcelona, SpainElias Campo - August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic of Barcelona, University of Barcelona, Barcelona, SpainJoseph F Fraumeni - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USASilvia de Sanjose - Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d’Oncologia, IDIBELL, Barcelona, SpainHenrik Hjalgrim - Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, DenmarkStephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USANathaniel Rothman - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USASusan L Slager - Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.45(8), pp.868-876
- DOI
- 10.1038/ng.2652
- PMID
- 23770605
- PMCID
- PMC3729927
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English
- Date published
- 08/2013
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984094370702771
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