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

  1. Author:
    McMaster, Mary L.
    Berndt, Sonja
    Zhang, Jianqing
    Slager, Susan L.
    Li,Shengchao
    Vajdic, Claire M.
    Smedby, Karin E.
    Yan, Huihuang
    Birmann, Brenda M.
    Brown, Elizabeth E.
    Smith, Alex
    Kleinstern, Geffen
    Fansler, Mervin M.
    Mayr, Christine
    Zhu,Bin
    Chung,Charles
    Park, Ju-Hyun
    Burdette, Laurie
    Hicks,Belynda
    Hutchinson,Amy
    Teras, Lauren R.
    Adami, Hans-Olov
    Bracci, Paige M.
    McKay, James
    Monnereau, Alain
    Link, Brian K.
    Vermeulen, Roel C. H.
    Ansell, Stephen M.
    Maria, Ann
    Diver, W. Ryan
    Melbye, Mads
    Ojesina, Akinyemi
    Kraft, Peter
    Boffetta, Paolo
    Clavel, Jacqueline
    Giovannucci, Edward
    Besson, Caroline M.
    Canzia, Federico
    Travis, Ruth C.
    Vineis, Paolo
    Weiderpass, Elisabete
    Montalvan, Rebecca
    Wang, Zhaoming
    Yeager,Meredith
    Becker, Nikolaus
    Benavente, Yolanda
    Brennan, Paul
    Foretova, Lenka
    Maynadie, Marc
    Nieters, Alexandra
    de Sanjose, Silvia
    Staines, Anthony
    Conde, Lucia
    Riby, Jacques
    Glimelius, Bengt
    Hjalgrim, Henrik
    Pradhan, Nisha
    Feldman, Andrew L.
    Novak, Anne J.
    Lawrence, Charles
    Bassig, Bryan A.
    Lan, Qing
    Zheng, Tongzhang
    North, Kari E.
    Tinker, Lesley F.
    Cozen, Wendy
    Severson, Richard K.
    Hofmann, Jonathan N.
    Zhang, Yawei
    Jackson, Rebecca D.
    Morton, Lindsay M.
    Purdue, Mark P.
    Chatterjee, Nilanjan
    Offit, Kenneth
    Cerhan, James R.
    Chanock, Stephen J.
    Rothman, Nathaniel
    Vijai, Joseph
    Goldin, Lynn R.
    Skibola, Christine F.
    Caporaso, Neil E.

  2. Author Address

    NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.Univ Alabama Birmingham, Comprehens Canc Ctr, Birmingham, AL 35233 USA.Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Genom Res Lab, Frederick, MD 20877 USA.Univ New South Wales, Ctr Big Data Res Hlth, Sydney, NSW 2052, Australia.Solna Karolinska Inst, Dept Med, S-17176 Stockholm, Sweden.Karolinska Univ Hosp, Hematol Ctr, S-17176 Stockholm, Sweden.Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.Harvard Med Sch, Boston, MA 02115 USA.Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35233 USA.Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.Weill Cornell Grad Coll, Triinst Training Program Computat Biol & Med, New York, NY 10021 USA.Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA.Dongguk Univ, Dept Stat, Seoul 100715, South Korea.Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.Univ Oslo, Inst Hlth & Soc, Clin Effectiveness Res Grp, NO-0316 Oslo, Norway.Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA.IARC, F-69372 Lyon, France.INSERM, Ctr Res Epidemiol & Stat Sorbonne Paris Cit CRESS, Epidemiol Childhood & Adolescent Canc Grp, F-94807 Paris, France.Univ Paris 05, F-75006 Paris, France.Univ Bordeaux, Inst Bergonie, Registry Hematol Malignancies Gironde, Team EPICENE,Inserm,UMR 1219, F-33000 Bordeaux, France.Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3584 CX Utrecht, Netherlands.Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA.Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.Statens Serum Inst, Dept Epidemiol Res, Div Hlth Surveillance & Res, DK-2300 Copenhagen, Denmark.Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.Inserm U1018, Ctr Rech Epidmiol St Populat CESP, Serv Hematol & Oncol, Ctr Hosp Versailles, F-78157 Villejuif, France.German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany.Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England.Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England.Human Genet Fdn, I-10126 Turin, Italy.Univ Tromso, Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, N-9019 Tromso, Norway.Canc Registry Norway, Dept Res, Inst Populat Based Canc Res, N-0379 Oslo, Norway.Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki 00250, Finland.Univ Adelaide, Helsinki 00250, Finland.Westat Corp, Rockville, MD 20850 USA.St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA.NCI, Div Canc Epidemiol & Genet, Lab Translat Genom, Bethesda, MD 20877 USA.German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Baden Wurttembe, Germany.Hosp Llobregat, Catalan Inst Oncol IDIBELL, Canc Epidemiol Res Programme, Barcelona 08908, Spain.CIBER Epidemiol & Salud Publ CIBERESP, Madrid 28029, Spain.Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic.MF MU, Brno 65653, Czech Republic.Univ Burgundy, EA 4184, Registre Hemopathies Malignes Cote dOr, F-21070 Dijon, France.Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Baden Wurttembe, Germany.Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland.UCL, Bill Lyons Informat Ctr, UCL Canc Inst, London WC1E 6DD, England.Univ Calif Berkeley, Div Environm Hlth Sci, Sch Publ Hlth, Berkeley, CA 94720 USA.Uppsala Univ, Dept Immunol Genet & Pathol, S-75105 Uppsala, Sweden.Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark.Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.Brown Univ, Dept Epidemiol, Providence, RI 02903 USA.Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98117 USA.Univ Southern Calif, USC Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.Univ Southern Calif, Norris Comprehens Canc Ctr, USC Keck Sch Med, Los Angeles, CA 90033 USA.Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA.Yale Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA.Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.Ontario Hlth Study, Toronto, ON M5S 1C6, Canada.Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.Emory Univ, Dept Hematol & Med Oncol, Sch Med, Atlanta, GA 30322 USA.
    1. Year: 2018
    2. Date: OCT 10
    3. Epub Date: 2018 10 10
  2. Journal: NATURE COMMUNICATIONS
  3. NATURE PUBLISHING GROUP,
    1. 9
    2. 1
    3. Pages: 4182
  5. Type of Article: Article
  6. Article Number: 4182
  7. ISSN: 2041-1723
  1. Abstract:

    Waldenstrom 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 x 10(-)(54)) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 x 10(-)(19)) . Both risk alleles are observed at a low frequency among controls (similar to 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.

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  2. DOI: 10.1038/s41467-018-06541-2
  3. PMID: 30305637
  4. View record in Web of Science®
  5. WOS: 000446846600001

Library Notes

  1. Fiscal Year: FY2018-2019
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