Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

Brian K Link; George J Weiner; James R Cerhan; Gilles Salles; Qing Lan; Gianluca Severi; Henrik Hjalgrim; Tracy Lightfoot; Mads Melbye; Jian Gu; Hervé Ghesquières; Lindsay M Morton; Elizabeth A Holly; Alex Smith; Lesley F Tinker; Lauren R Teras; Anne Kricker; Nikolaus Becker; Mark P Purdue; John J Spinelli; Yawei Zhang; Graham G Giles; Paolo Vineis; Christine F Skibola; Alain Monnereau; Paul I W de Bakker; Kimberly A Bertrand; Liming Liang; Demetrius Albanes; Brenda M Birmann; Sonja I Berndt; Anne Zeleniuch-Jacquotte; Jinyan Huang; Ahmet Dogan; Baoshan Ma; Attilio Gabbas; Joseph Vijai; Charles C Chung; Claire M Vajdic; Laurie Burdett; Jianjun Liu; Amy Hutchinson; Jia-Nee Foo; Lucia Conde; Zhaoming Wang; Charles Lawrence; Hans-Olov Adami; Paige M Bracci; Meredith Yeager; Rebecca Montalvan; Roel C H Vermeulen; Bengt Glimelius; Susan L Slager; Yuanqing Ye; Grzegorz S Nowakowski; Silvia de Sanjose; Sophia S Wang; Carrie A Thompson; Anne J Novak; Martha S Linet; Thomas M Habermann; Mark Liebow; Thomas E Witzig; Maryjean Schenk; Patricia Hartge; Anneclaire J De Roos; Wendy Cozen; Degui Zhi; Nicholas K Akers; Jacques Riby; Martyn T Smith; Mortimer Lacher; Danylo J Villano; Ann Maria; Eve Roman; Eleanor Kane; Rebecca D Jackson; Kari E North; W Ryan Diver; Jenny Turner; Bruce K Armstrong; Yolanda Benavente; Paolo Boffetta; Paul Brennan; Lenka Foretova; Marc Maynadie; Anthony Staines; James McKay; Angela R Brooks-Wilson; Tongzhang Zheng; Theodore R Holford; Saioa Chamosa; Rudolph Kaaks; Rachel S Kelly; Bodil Ohlsson; Ruth C Travis; Elisabete Weiderpass; Jacqueline Clavel; Edward Giovannucci; Peter Kraft; Jarmo Virtamo; Patrizio Mazza; Pierluigi Cocco; Maria Grazia Ennas; Brian C H Chiu; Joseph F Fraumeni Jr; Alexandra Nieters; Kenneth Offit; Xifeng Wu; Karin E Smedby; Stephen J Chanock; Nathaniel Rothman

doi:10.1016/j.ajhg.2014.09.004

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Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

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Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region

Brian K Link, George J Weiner, James R Cerhan, Gilles Salles, Qing Lan, Gianluca Severi, Henrik Hjalgrim, Tracy Lightfoot, Mads Melbye, Jian Gu, …

American journal of human genetics, Vol.95(4), pp.462-471

10/02/2014

DOI: 10.1016/j.ajhg.2014.09.004

PMCID: PMC4185120

PMID: 25279986

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Abstract

Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.

Haplotypes - genetics

Genetic Predisposition to Disease

Genome-Wide Association Study

Lymphoma, Follicular - genetics

Chromosomes, Human - genetics

Humans

Alleles

Polymorphism, Single Nucleotide - genetics

Biomarkers, Tumor - genetics

HLA Antigens - genetics

Case-Control Studies

Details

Title: Subtitle: Genome-wide association study identifies five susceptibility loci for follicular lymphoma outside the HLA region
Creators: Brian K Link - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
George J Weiner - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
James R Cerhan - Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
Gilles Salles - Department of Hematology, Hospices Civils de Lyon, Pierre benite Cedex 69495, France; Department of Hematology, Université Lyon-1, Pierre benite Cedex 69495, France; Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex 69495, France
Qing Lan - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Gianluca Severi - Human Genetics Foundation, Turin 10126, Italy; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3053, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC 3010, Australia
Henrik Hjalgrim - Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark
Tracy Lightfoot - Department of Health Sciences, University of York, York YO10 5DD, UK
Mads Melbye - Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen 2300, Denmark; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Jian Gu - Department of Epidemiology, M.D. Anderson Cancer Center, Houston, TX 77030, USA
Hervé Ghesquières - Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex 69495, France; Department of Hematology, Centre Léon Bérard, Lyon 69008, France
Lindsay M Morton - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Elizabeth A Holly - Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA 94118, USA
Alex Smith - Department of Health Sciences, University of York, York YO10 5DD, UK
Lesley F Tinker - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98117, USA
Lauren R Teras - Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA
Anne Kricker - Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia
Nikolaus Becker - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg 69120, Germany
Mark P Purdue - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
John J Spinelli - Cancer Control Research, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Yawei Zhang - Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA
Graham G Giles - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC 3053, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Carlton, VIC 3010, Australia
Paolo Vineis - Human Genetics Foundation, Turin 10126, Italy; MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK
Christine F Skibola - Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, AL 35233, USA; Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA. Electronic address: cskibola@uab.edu
Alain Monnereau - Environmental Epidemiology of Cancer Group, Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif Cedex 94807, France; UMRS 1018, Université Paris Sud, Villejuif Cedex 94807, France; Registre des hémopathies malignes de la Gironde, Institut Bergonié, Bordeaux Cedex 33076, France
Paul I W de Bakker - Department of Medical Genetics and of Epidemiology, University Medical Center Utrecht, Utrecht 3584 CG, the Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands
Kimberly A Bertrand - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
Liming Liang - Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
Brenda M Birmann - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Sonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Demetrius Albanes - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Anne Zeleniuch-Jacquotte - Department of Population Health, New York University School of Medicine, New York, NY 10016, USA; Cancer Institute, New York University School of Medicine, New York, NY 10016, USA
Jinyan Huang - Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
Ahmet Dogan - Departments of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Attilio Gabbas - Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari 09042, Italy
Baoshan Ma - Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning Province 116026, China
Joseph Vijai - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Charles C Chung - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Claire M Vajdic - Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052, Australia
Laurie Burdett - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Gaithersburg, MD 20877, USA
Jianjun Liu - Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore
Amy Hutchinson - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Gaithersburg, MD 20877, USA
Jia-Nee Foo - Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore
Lucia Conde - Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, AL 35233, USA; Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA
Charles Lawrence - Health Studies Sector, Westat, Rockville, MD 20850, USA
Zhaoming Wang - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Gaithersburg, MD 20877, USA
Hans-Olov Adami - Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden
Meredith Yeager - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Gaithersburg, MD 20877, USA
Rebecca Montalvan - Health Studies Sector, Westat, Rockville, MD 20850, USA
Paige M Bracci - Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA 94118, USA
Roel C H Vermeulen - Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands; Institute for Risk Assessment Sciences, Utrecht University, Utrecht 3508 TD, the Netherlands
Bengt Glimelius - Department of Oncology and Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm 17176, Sweden; Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala 75105, Sweden
Susan L Slager - Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
Yuanqing Ye - Department of Epidemiology, M.D. Anderson Cancer Center, Houston, TX 77030, USA
Grzegorz S Nowakowski - Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
Silvia de Sanjose - Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, Barcelona 8907, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona 8036, Spain
Sophia S Wang - Department of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, CA 91030, USA
Carrie A Thompson - Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Anne J Novak - Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Martha S Linet - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Thomas M Habermann - Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Mark Liebow - Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Thomas E Witzig - Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
Maryjean Schenk - Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI 48201, USA
Patricia Hartge - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Anneclaire J De Roos - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98117, USA; Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, PA 19104, USA
Wendy Cozen - 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
Degui Zhi - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35233, USA
Nicholas K Akers - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA
Jacques Riby - Department of Epidemiology, School of Public Health and Comprehensive Cancer Center, Birmingham, AL 35233, USA; Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA
Martyn T Smith - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA 94720, USA
Mortimer Lacher - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Danylo J Villano - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Ann Maria - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Eve Roman - Department of Health Sciences, University of York, York YO10 5DD, UK
Eleanor Kane - Department of Health Sciences, University of York, York YO10 5DD, UK
Rebecca D Jackson - Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH 43210, USA
Kari E North - 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
W Ryan Diver - Epidemiology Research Program, American Cancer Society, Atlanta, GA 30303, USA
Jenny Turner - Department of Anatomical Pathology, Australian School of Advanced Medicine, Macquarie University, Sydney, NSW 2109, Australia; Department of Histopathology, Douglass Hanly Moir Pathology, Macquarie Park, NSW 2113, Australia
Bruce K Armstrong - Sydney School of Public Health, The University of Sydney, Sydney, NSW 2006, Australia
Yolanda Benavente - Unit of Infections and Cancer (UNIC), Cancer Epidemiology Research Programme, Institut Catala d'Oncologia, IDIBELL, Barcelona 8907, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Barcelona 8036, Spain
Paolo Boffetta - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Paul Brennan - Group of Genetic Epidemiology, Section of Genetics, International Agency for Research on Cancer, Lyon 69372, France
Lenka Foretova - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno 656 53, Czech Republic
Marc Maynadie - EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon 21070, France
Anthony Staines - School of Nursing and Human Sciences, Dublin City University, Dublin 9, Ireland
James McKay - Genetic Cancer Susceptibility Group, Section of Genetics, International Agency for Research on Cancer, Lyon 69372, France
Angela R Brooks-Wilson - Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC V5A 1S6, Canada
Tongzhang Zheng - Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06520, USA
Theodore R Holford - Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520, USA
Saioa Chamosa - Health Department, BioDonostia Research Institute, Basque Region 20014, Spain
Rudolph Kaaks - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg 69120, Germany
Rachel S Kelly - MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
Bodil Ohlsson - Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö 205 02, Sweden
Ruth C Travis - Cancer Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK
Elisabete Weiderpass - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden; Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Breivika 9037, Norway; Cancer Registry of Norway, Oslo 0304, Norway; Department of Genetic Epidemiology, Folkhalsan Research Center, Helsinki 00250, Finland
Jacqueline Clavel - Environmental Epidemiology of Cancer Group, Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif Cedex 94807, France; UMRS 1018, Université Paris Sud, Villejuif Cedex 94807, France
Edward Giovannucci - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA
Peter Kraft - Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
Jarmo Virtamo - Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki 00271, Finland
Patrizio Mazza - Department of Hematology, Ospedale Nord, Taranto 74100, Italy
Pierluigi Cocco - Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari 09042, Italy
Maria Grazia Ennas - Department of Biomedical Science, University of Cagliari, Monserrato, Cagliari 09042, Italy
Brian C H Chiu - Department of Health Studies, University of Chicago, Chicago, IL 60637, USA
Joseph F Fraumeni Jr - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Alexandra Nieters - Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg 79108, Germany
Kenneth Offit - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Xifeng Wu - Department of Epidemiology, M.D. Anderson Cancer Center, Houston, TX 77030, USA
Karin E Smedby - Department of Medicine Solna, Karolinska Institutet, Stockholm 17176, Sweden
Stephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Nathaniel Rothman - Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Resource Type: Journal article
Publication Details: American journal of human genetics, Vol.95(4), pp.462-471
DOI: 10.1016/j.ajhg.2014.09.004
PMID: 25279986
PMCID: PMC4185120
ISSN: 0002-9297
eISSN: 1537-6605
Grant note: UL1 TR000142 / NCATS NIH HHS R01 CA154643 / NCI NIH HHS P30 CA033572 / NCI NIH HHS L30 CA162082 / NCI NIH HHS UL1 TR000430 / NCATS NIH HHS P42 ES004705 / NIEHS NIH HHS P30 CA008748 / NCI NIH HHS P30 CA086862 / NCI NIH HHS P30 CA015083 / NCI NIH HHS P50 CA097274 / NCI NIH HHS R01 CA149445 / NCI NIH HHS Intramural NIH HHS P30 CA016672 / NCI NIH HHS P30 ES010126 / NIEHS NIH HHS P30 CA016359 / NCI NIH HHS
Language: English
Date published: 10/02/2014
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
Record Identifier: 9984094218102771

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