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

Mitchell J Machiela; Brian K Link; 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; 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 Jr; 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

doi:10.1093/hmg/ddw027

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

Journal article

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

Mitchell J Machiela, Brian K Link, Qing Lan, Susan L Slager, Roel C H Vermeulen, Lauren R Teras, Nicola J Camp, James R Cerhan, John J Spinelli, Sophia S Wang, …

Human molecular genetics, Vol.25(8), pp.1663-1676

04/15/2016

DOI: 10.1093/hmg/ddw027

PMCID: PMC4854019

PMID: 27008888

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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 length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.

Genetic Predisposition to Disease

Prospective Studies

Age Factors

Humans

Middle Aged

Genetic Association Studies - methods

Male

Lymphoma, B-Cell - genetics

Telomere - pathology

Adolescent

Lymphoma, B-Cell - pathology

Aged, 80 and over

Adult

Female

Aged

Details

Title: Subtitle: Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes
Creators: Mitchell J Machiela - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, mitchell.machiela@nih.gov
Brian K Link - Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Qing Lan - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Susan L Slager - Department of Health Sciences Research
Roel C H Vermeulen - Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands, Julius Center for Health Sciences and Primary Care and
Lauren R Teras - Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
Nicola J Camp - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
James R Cerhan - Department of Health Sciences Research
John J Spinelli - Cancer Control Research and School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
Sophia S Wang - Division of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, CA, USA
Alexandra Nieters - Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany
Joseph Vijai - Department of Medicine and
Meredith Yeager - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA
Zhaoming Wang - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA
Hervé Ghesquières - Department of Hematology and Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex, France
James McKay - International Agency for Research on Cancer (IARC), Lyon, France
Lucia Conde - Department of Epidemiology, School of Public Health and Comprehensive Cancer Center and Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA, USA
Paul I W de Bakker - Julius Center for Health Sciences and Primary Care and Department of Medical Genetics and of Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands
David G Cox - INSERM U1052, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon, France
Laurie Burdett - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA
Alain Monnereau - Epidemiology of Childhood and Adolescent Cancers Group, INSERM, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France, Université Paris Descartes, Paris, France, Registre des hémopathies malignes de la Gironde, Institut Bergonié, Bordeaux Cedex, France
Christopher R Flowers - Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA
Anneclaire J De Roos - Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, PA, USA, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Angela R Brooks-Wilson - Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada, Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada
Graham G Giles - Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health and
Mads Melbye - Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
Jian Gu - Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA
Rebecca D Jackson - Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH, USA
Eleanor Kane - Department of Health Sciences, University of York, York, UK
Mark P Purdue - Ontario Health Study, Toronto, ON, Canada
Claire M Vajdic - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia
Demetrius Albanes - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Rachel S Kelly - Department of Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health and
Mariagrazia Zucca - Department of Biomedical Science and
Kimberly A Bertrand - Department of Epidemiology, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Anne Zeleniuch-Jacquotte - Department of Population Health and Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA, Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, USA
Charles Lawrence - Westat, Rockville, MD, USA
Amy Hutchinson - Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA
Degui Zhi - Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA
Thomas M Habermann - Department of Medicine and
Anne J Novak - Department of Medicine and
Ahmet Dogan - Departments of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Yan W Asmann - Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA
Mark Liebow - Department of Medicine and
Carrie A Thompson - Department of Medicine and
Stephen M Ansell - Department of Medicine and
Thomas E Witzig - Department of Medicine and
Hervé Tilly - Centre Heni Becquerel, Université de Rouen, Rouen, France
Corinne Haioun - Lymphoid Malignancies Unit, Henri Mondor Hospital and University Paris Est, Créteil, France
Thierry J Molina - Department of Pathology, AP-HP, Necker Enfants malades, Université Paris Descartes, Sorbonne Paris Cité, France
Henrik Hjalgrim - Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark
Bengt Glimelius - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Hans-Olov Adami - Department of Epidemiology, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Göran Roos - Department of Medical Biosciences, Umeå University, Umeå, Sweden
Paige M Bracci - Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
Jacques Riby - Department of Epidemiology, School of Public Health and Comprehensive Cancer Center and Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA, USA
Martyn T Smith - Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA, USA
Elizabeth A Holly - Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
Wendy Cozen - Department of Preventive Medicine and Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Patricia Hartge - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Lindsay M Morton - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Richard K Severson - Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI, USA
Lesley F Tinker - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Kari E North - Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Nikolaus Becker - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany
Yolanda Benavente - Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Paolo Boffetta - The Tisch Cancer Institute and
Paul Brennan - International Agency for Research on Cancer (IARC), Lyon, France
Lenka Foretova - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic
Marc Maynadie - EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, France
Anthony Staines - School of Nursing and Human Sciences, Dublin City University, Dublin, Ireland
Tracy Lightfoot - Department of Health Sciences, University of York, York, UK
Simon Crouch - Department of Health Sciences, University of York, York, UK
Alex Smith - Department of Health Sciences, University of York, York, UK
Eve Roman - Department of Health Sciences, University of York, York, UK
W Ryan Diver - Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA
Kenneth Offit - Department of Medicine and
Andrew Zelenetz - Department of Medicine and
Robert J Klein - Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Danylo J Villano - Department of Medicine and
Tongzhang Zheng - Department of Environmental Health Sciences and
Yawei Zhang - Department of Environmental Health Sciences and
Theodore R Holford - Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA
Jenny Turner - Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia, Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, NSW, Australia
Melissa C Southey - Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, VIC, Australia
Jacqueline Clavel - Epidemiology of Childhood and Adolescent Cancers Group, INSERM, Center of Research in Epidemiology and Statistics Sorbonne Paris Cité (CRESS), Paris, France, Université Paris Descartes, Paris, France
Jarmo Virtamo - Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland
Stephanie Weinstein - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Elio Riboli - School of Public Health, Imperial College London, London, UK
Paolo Vineis - MRC-PHE Centre for Environment and Health, School of Public Health and Human Genetics Foundation, Turin, Italy
Rudolph Kaaks - Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany
Heiner Boeing - Department of Epidemiology, German Institute for Human Nutrition, Potsdam, Germany
Anne Tjønneland - Danish Cancer Society Research Center, Copenhagen, Denmark
Emanuele Angelucci - Hematology Unit, Ospedale Oncologico di Riferimento Regionale A. Businco, Cagliari, Italy
Simonetta Di Lollo - Department of Surgery and Translational Medicine, Section of Anatomo-Pathology, University of Florence, Florence, Italy
Marco Rais - Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari, Italy
Immaculata De Vivo - Department of Epidemiology, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Edward Giovannucci - Department of Epidemiology, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Department of Nutrition and
Peter Kraft - Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
Jinyan Huang - Department of Epidemiology
Baoshan Ma - Department of Epidemiology, College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning Province, China
Yuanqing Ye - Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA
Brian C H Chiu - Department of Health Studies, University of Chicago, Chicago, IL, USA
Liming Liang - Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
Ju-Hyun Park - Department of Statistics, Dongguk University, Seoul, Republic of Korea
Charles C Chung - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Dennis D Weisenburger - Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA
Joseph F Fraumeni Jr - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Gilles Salles - Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex, France, Department of Hematology, Hospices Civils de Lyon, Pierre benite Cedex, France, Department of Hematology, Université Lyon-1, Pierre benite Cedex, France and
Martha Glenn - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
Lisa Cannon-Albright - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
Karen Curtin - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
Xifeng Wu - Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA
Karin E Smedby - Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
Silvia de Sanjose - Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
Christine F Skibola - Department of Epidemiology, School of Public Health and Comprehensive Cancer Center and Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA, USA
Sonja I Berndt - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Brenda M Birmann - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Stephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Nathaniel Rothman - Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Resource Type: Journal article
Publication Details: Human molecular genetics, Vol.25(8), pp.1663-1676
Publisher: England
DOI: 10.1093/hmg/ddw027
PMID: 27008888
PMCID: PMC4854019
ISSN: 0964-6906
eISSN: 1460-2083
Grant note: R01 CA092153 / NCI NIH HHS U58 DP000807 / NCCDPHP CDC HHS R01 CA154643 / NCI NIH HHS HHSN268201100004I / NHLBI NIH HHS CA87969 / NCI NIH HHS R01 CA062006 / NCI NIH HHS R01 CA92153 / NCI NIH HHS ES000260 / NIEHS NIH HHS U01 CA049449 / NCI NIH HHS HHSN268201100004C / WHI NIH HHS R01 CA098122 / NCI NIH HHS Intramural NIH HHS CA134674 / NCI NIH HHS HHSN261201000006C / NCI NIH HHS HHSN268201100002C / WHI NIH HHS N01-PC-67009 / NCI NIH HHS HHSN261201000035C / NCI NIH HHS CA1046282 / NCI NIH HHS N01CO12400 / NCI NIH HHS R35 CA197449 / NCI NIH HHS HHSN268201100003C / WHI NIH HHS P50 CA97274 / NCI NIH HHS P30 ES000260 / NIEHS NIH HHS N02-PC-71105 / NCI NIH HHS UL1 TR000135 / NCATS NIH HHS N01-CO-12400 / NCI NIH HHS P01 CA087969 / NCI NIH HHS K08 CA134919 / NCI NIH HHS CA098122 / NCI NIH HHS HHSN268201100046C / NHLBI NIH HHS R25 CA098566 / NCI NIH HHS R01 CA134674 / NCI NIH HHS P30 CA042014 / NCI NIH HHS P30 CA016359 / NCI NIH HHS CA49449 / NCI NIH HHS 5R01 CA69669-02 / NCI NIH HHS HHSN261201000035I / NCI NIH HHS CA098566 / NCI NIH HHS HHSN271201100004C / NIA NIH HHS U01 HG007033 / NHGRI NIH HHS CA154643 / NCI NIH HHS CA165923 / NCI NIH HHS N01 PC067008 / NCI NIH HHS N01 PC065064 / NCI NIH HHS P30 CA015083 / NCI NIH HHS P50 CA097274 / NCI NIH HHS CA149445 / NCI NIH HHS K08CA134919 / NCI NIH HHS UL1 TR001070 / NCATS NIH HHS HHSN261201000140C / NCI NIH HHS P30 CA42014 / NCI NIH HHS R01 CA148690 / NCI NIH HHS UL1 TR001863 / NCATS NIH HHS #1U58 DP000807-01 / NCCDPHP CDC HHS N01-RC-45035 / CCR NIH HHS R01 CA098661 / NCI NIH HHS UM1 CA167552 / NCI NIH HHS HHSN268201100002I / NHLBI NIH HHS N01 PC067010 / NCI NIH HHS HHSN268201100001C / WHI NIH HHS CA92153 / NCI NIH HHS CIHR HHSN261201000034C / NCI NIH HHS N01 CN045165 / NCI NIH HHS P30 CA008748 / NCI NIH HHS P30 CA086862 / NCI NIH HHS UM1 CA186107 / NCI NIH HHS CA167552 / NCI NIH HHS CA118444 / NCI NIH HHS K07 CA115687 / NCI NIH HHS R01 CA149445 / NCI NIH HHS Cancer Research UK HHSN268201100001I / NHLBI NIH HHS R01 CA049449 / NCI NIH HHS CA148690 / NCI NIH HHS U01 CA118444 / NCI NIH HHS CA186107 / NCI NIH HHS R21 CA165923 / NCI NIH HHS N01RC37004 / CCR NIH HHS HHSN261201000026C / NCI NIH HHS P30 CA016087 / NCI NIH HHS N01 PC067009 / NCI NIH HHS
Language: English
Date published: 04/15/2016
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
Record Identifier: 9984071699702771

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