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Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

  • Mitchell J. Machiela
  • , Qing Lan
  • , Susan L. Slager
  • , Roel C.H. Vermeulen
  • , Lauren R. Teras
  • , Nicola J. Camp
  • , James R. Cerhan
  • , John J. Spinelli
  • , Sophia S. Wang
  • , Alexandra Nieters
  • , Joseph Vijai
  • , Meredith Yeager
  • , Zhaoming Wang
  • , Hervé Ghesquières
  • , James McKay
  • , Lucia Conde
  • , Paul I.W. de Bakker
  • , David G. Cox
  • , Laurie Burdett
  • , Alain Monnereau
  • Christopher R. Flowers, Anneclaire J. De Roos, Angela R. Brooks-Wilson, Graham G. Giles, Mads Melbye, Jian Gu, Rebecca D. Jackson, Eleanor Kane, Mark P. Purdue, Claire M. Vajdic, Demetrius Albanes, Rachel S. Kelly, Mariagrazia Zucca, Kimberly A. Bertrand, Anne Zeleniuch-Jacquotte, Charles Lawrence, Amy Hutchinson, Degui Zhi, Thomas M. Habermann, Brian K. Link, Anne J. Novak, Ahmet Dogan, Yan W. Asmann, Mark Liebow, Carrie A. Thompson, Stephen M. Ansell, Thomas E. Witzig, Hervé Tilly, Corinne Haioun, Thierry J. Molina, Henrik Hjalgrim, Bengt Glimelius, Hans Olov Adami, Göran Roos, Paige M. Bracci, Jacques Riby, Martyn T. Smith, Elizabeth A. Holly, Wendy Cozen, Patricia Hartge, Lindsay M. Morton, Richard K. Severson, Lesley F. Tinker, Kari E. North, Nikolaus Becker, Yolanda Benavente, Paolo Boffetta, Paul Brennan, Lenka Foretova, Marc Maynadie, Anthony Staines, Tracy Lightfoot, Simon Crouch, Alex Smith, Eve Roman, W. Ryan Diver, Kenneth Offit, Andrew Zelenetz, Robert J. Klein, Danylo J. Villano, Tongzhang Zheng, Yawei Zhang, Theodore R. Holford, Jenny Turner, Melissa C. Southey, Jacqueline Clavel, Jarmo Virtamo, Stephanie Weinstein, Elio Riboli, Paolo Vineis, Rudolph Kaaks, Heiner Boeing, Anne Tjønneland, Emanuele Angelucci, Simonetta Di Lollo, Marco Rais, Immaculata De Vivo, Edward Giovannucci, Peter Kraft, Jinyan Huang, Baoshan Ma, Yuanqing Ye, Brian C.H. Chiu, Liming Liang, Ju Hyun Park, Charles C. Chung, Dennis D. Weisenburger, Joseph F. Fraumeni, Gilles Salles, Martha Glenn, Lisa Cannon-Albright, Karen Curtin, Xifeng Wu, Karin E. Smedby, Silvia de Sanjose, Christine F. Skibola, Sonja I. Berndt, Brenda M. Birmann, Stephen J. Chanock, Nathaniel Rothman
  • National Institutes of Health
  • Mayo Clinic Rochester, MN
  • Utrecht University
  • American Cancer Society
  • University of Utah
  • Provincial Health Services Authority
  • University of British Columbia
  • City of Hope National Med Center
  • University of Freiburg
  • Memorial Sloan-Kettering Cancer Center
  • Centre Léon Bérard
  • CNRS
  • International Agency for Research on Cancer
  • University of Alabama at Birmingham
  • University of California at Berkeley
  • Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS)
  • Université Paris Cité
  • Centre Georges-François Leclerc
  • Emory University
  • Drexel University
  • Fred Hutchinson Cancer Research Center
  • Simon Fraser University
  • Cancer Council Victoria
  • University of Melbourne
  • Statens Serum Institut
  • Stanford University
  • University of Texas MD Anderson Cancer Center
  • Ohio State University
  • University of York
  • Ontario Health
  • University of New South Wales
  • Harvard University
  • School of Public Health
  • University of Cagliari
  • Brigham and Women’s Hospital
  • New York University
  • Westat
  • University of Iowa
  • Université de Rouen Normandie
  • Hôpital Henri Mondor
  • Uppsala University
  • Karolinska Institutet
  • Umeå University
  • University of California at San Francisco
  • University of Southern California
  • Wayne State University
  • University of North Carolina at Chapel Hill
  • German Cancer Research Center
  • L'Hospitalet de Llobregat
  • Centro de Investigacion Biomedica en Red CIBER Epidemiologia y Salud Publica
  • Icahn School of Medicine at Mount Sinai
  • Masaryk Memorial Cancer Institute
  • Université de Bourgogne
  • Dublin City University
  • Yale University
  • Macquarie University
  • Sonic Healthcare
  • National Institute for Health and Welfare
  • Imperial College London
  • Human Genetics Foundation
  • German Institute of Human Nutrition Potsdam-Rehbruecke
  • Danish Cancer Society
  • AO Brotzu
  • University of Florence
  • Dalian Maritime University
  • The University of Chicago
  • Hospices civils de Lyon
  • Universite Claude Bernard Lyon 1

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk.We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82, P-value = 8.5 × 10-5]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51, P-value = 4.0 × 10-10). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere lengthmay increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

Original languageEnglish
Pages (from-to)1663-1676
Number of pages14
JournalHuman Molecular Genetics
Volume25
Issue number8
DOIs
StatePublished - 15 Apr 2016

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