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Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

Author

Listed:
  • Mary L. McMaster

    (National Cancer Institute)

  • Sonja I. Berndt

    (National Cancer Institute)

  • Jianqing Zhang

    (University of Alabama at Birmingham)

  • Susan L. Slager

    (Mayo Clinic)

  • Shengchao Alfred Li

    (Frederick National Lab for Cancer Research)

  • Claire M. Vajdic

    (University of New South Wales)

  • Karin E. Smedby

    (Solna Karolinska Institutet
    Karolinska University Hospital)

  • Huihuang Yan

    (Mayo Clinic)

  • Brenda M. Birmann

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Elizabeth E. Brown

    (University of Alabama at Birmingham)

  • Alex Smith

    (University of York)

  • Geffen Kleinstern

    (Mayo Clinic)

  • Mervin M. Fansler

    (Weill Cornell Graduate College
    Memorial Sloan Kettering Cancer Center)

  • Christine Mayr

    (Memorial Sloan Kettering Cancer Center)

  • Bin Zhu

    (Frederick National Lab for Cancer Research)

  • Charles C. Chung

    (Frederick National Lab for Cancer Research)

  • Ju-Hyun Park

    (Dongguk University)

  • Laurie Burdette

    (Frederick National Lab for Cancer Research)

  • Belynda D. Hicks

    (Frederick National Lab for Cancer Research)

  • Amy Hutchinson

    (Frederick National Lab for Cancer Research)

  • Lauren R. Teras

    (American Cancer Society)

  • Hans-Olov Adami

    (Karolinska Institutet
    Harvard T.H. Chan School of Public Health
    University of Oslo)

  • Paige M. Bracci

    (University of California, San Francisco)

  • James McKay

    (International Agency for Research on Cancer (IARC))

  • Alain Monnereau

    (Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS)
    Université Paris Descartes
    UMR 1219)

  • Brian K. Link

    (The University of Iowa)

  • Roel C. H. Vermeulen

    (Utrecht University
    University Medical Center Utrecht)

  • Stephen M. Ansell

    (Mayo Clinic)

  • Ann Maria

    (Memorial Sloan Kettering Cancer Center)

  • W. Ryan Diver

    (American Cancer Society)

  • Mads Melbye

    (Statens Serum Institut
    Stanford University School of Medicine)

  • Akinyemi I. Ojesina

    (University of Alabama at Birmingham)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Paolo Boffetta

    (Icahn School of Medicine at Mount Sinai)

  • Jacqueline Clavel

    (Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS)
    Université Paris Descartes)

  • Edward Giovannucci

    (Brigham and Women’s Hospital and Harvard Medical School
    Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Caroline M. Besson

    (Centre pour la Recherche en Epidémiologie et Santé des Populations (CESP))

  • Federico Canzian

    (German Cancer Research Center (DKFZ))

  • Ruth C. Travis

    (University of Oxford)

  • Paolo Vineis

    (Imperial College London
    Human Genetics Foundation)

  • Elisabete Weiderpass

    (Karolinska Institutet
    The Arctic University of Norway
    Institute of Population-Based Cancer Research
    Folkhälsan Research Center and University of Helsinki)

  • Rebecca Montalvan

    (Westat)

  • Zhaoming Wang

    (St. Jude Children’s Research Hospital
    National Cancer Institute)

  • Meredith Yeager

    (Frederick National Lab for Cancer Research)

  • Nikolaus Becker

    (German Cancer Research Center (DKFZ))

  • Yolanda Benavente

    (L’Hospitalet de Llobregat
    CIBER Epidemiología y Salud Pública (CIBERESP))

  • Paul Brennan

    (International Agency for Research on Cancer (IARC))

  • Lenka Foretova

    (Masaryk Memorial Cancer Institute and MF MU)

  • Marc Maynadie

    (University of Burgundy and Dijon University Hospital)

  • Alexandra Nieters

    (University Medical Center Freiburg)

  • Silvia Sanjose

    (L’Hospitalet de Llobregat
    CIBER Epidemiología y Salud Pública (CIBERESP))

  • Anthony Staines

    (Dublin City University)

  • Lucia Conde

    (University College London)

  • Jacques Riby

    (University of Alabama at Birmingham
    University of California Berkeley School of Public Health)

  • Bengt Glimelius

    (Uppsala University)

  • Henrik Hjalgrim

    (Statens Serum Institut
    Rigshospitalet)

  • Nisha Pradhan

    (Memorial Sloan Kettering Cancer Center)

  • Andrew L. Feldman

    (Mayo Clinic)

  • Anne J. Novak

    (Mayo Clinic)

  • Charles Lawrence

    (Westat)

  • Bryan A. Bassig

    (National Cancer Institute)

  • Qing Lan

    (National Cancer Institute)

  • Tongzhang Zheng

    (Brown University)

  • Kari E. North

    (University of North Carolina at Chapel Hill
    University of North Carolina at Chapel Hill)

  • Lesley F. Tinker

    (Fred Hutchinson Cancer Research Center)

  • Wendy Cozen

    (University of Southern California
    University of Southern California)

  • Richard K. Severson

    (Wayne State University)

  • Jonathan N. Hofmann

    (National Cancer Institute)

  • Yawei Zhang

    (Yale School of Public Health)

  • Rebecca D. Jackson

    (The Ohio State University)

  • Lindsay M. Morton

    (National Cancer Institute)

  • Mark P. Purdue

    (National Cancer Institute
    Ontario Health Study)

  • Nilanjan Chatterjee

    (National Cancer Institute
    Johns Hopkins University
    Johns Hopkins University)

  • Kenneth Offit

    (Memorial Sloan Kettering Cancer Center)

  • James R. Cerhan

    (Mayo Clinic)

  • Stephen J. Chanock

    (National Cancer Institute)

  • Nathaniel Rothman

    (National Cancer Institute)

  • Joseph Vijai

    (Memorial Sloan Kettering Cancer Center)

  • Lynn R. Goldin

    (National Cancer Institute)

  • Christine F. Skibola

    (Emory University School of Medicine)

  • Neil E. Caporaso

    (National Cancer Institute)

Abstract

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10−54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10−19). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

Suggested Citation

  • Mary L. McMaster & Sonja I. Berndt & Jianqing Zhang & Susan L. Slager & Shengchao Alfred Li & Claire M. Vajdic & Karin E. Smedby & Huihuang Yan & Brenda M. Birmann & Elizabeth E. Brown & Alex Smith & , 2018. "Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06541-2
    DOI: 10.1038/s41467-018-06541-2
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