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Hum Mol Genet. 2016 Apr 15;25(8):1663-76. doi: 10.1093/hmg/ddw027. Epub 2016 Feb 9.

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

Machiela MJ1, Lan Q2, Slager SL3, Vermeulen RC4, Teras LR5, Camp NJ6, Cerhan JR3, Spinelli JJ7, Wang SS8, Nieters A9, Vijai J10, Yeager M11, Wang Z11, Ghesquières H12, McKay J13, Conde L14, de Bakker PI15, Cox DG16, Burdett L11, Monnereau A17, Flowers CR18, De Roos AJ19, Brooks-Wilson AR20, Giles GG21, Melbye M22, Gu J23, Jackson RD24, Kane E25, Purdue MP26, Vajdic CM27, Albanes D2, Kelly RS28, Zucca M29, Bertrand KA30, Zeleniuch-Jacquotte A31, Lawrence C32, Hutchinson A11, Zhi D33, Habermann TM10, Link BK34, Novak AJ10, Dogan A35, Asmann YW36, Liebow M10, Thompson CA10, Ansell SM10, Witzig TE10, Tilly H37, Haioun C38, Molina TJ39, Hjalgrim H40, Glimelius B41, Adami HO42, Roos G43, Bracci PM44, Riby J14, Smith MT45, Holly EA44, Cozen W46, Hartge P2, Morton LM2, Severson RK47, Tinker LF48, North KE49, Becker N50, Benavente Y51, Boffetta P52, Brennan P13, Foretova L53, Maynadie M54, Staines A55, Lightfoot T25, Crouch S25, Smith A25, Roman E25, Diver WR5, Offit K10, Zelenetz A10, Klein RJ56, Villano DJ10, Zheng T57, Zhang Y57, Holford TR58, Turner J59, Southey MC60, Clavel J61, Virtamo J62, Weinstein S2, Riboli E63, Vineis P64, Kaaks R50, Boeing H65, Tjønneland A66, Angelucci E67, Di Lollo S68, Rais M69, De Vivo I30, Giovannucci E70, Kraft P71, Huang J72, Ma B73, Ye Y23, Chiu BC74, Liang L71, Park JH75, Chung CC2, Weisenburger DD76, Fraumeni JF Jr2, Salles G77, Glenn M6, Cannon-Albright L6, Curtin K6, Wu X23, Smedby KE78, de Sanjose S51, Skibola CF14, Berndt SI2, Birmann BM79, Chanock SJ2, Rothman N2.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, mitchell.machiela@nih.gov.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
3
Department of Health Sciences Research.
4
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands, Julius Center for Health Sciences and Primary Care and.
5
Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
6
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
7
Cancer Control Research and School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
8
Division of Cancer Etiology, City of Hope Beckman Research Institute, Duarte, CA, USA.
9
Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Baden-Württemberg, Germany.
10
Department of Medicine and.
11
Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD, USA.
12
Department of Hematology and Laboratoire de Biologie Moléculaire de la Cellule UMR 5239, Centre National de la Recherche Scientifique, Pierre benite Cedex, France.
13
International Agency for Research on Cancer (IARC), Lyon, France.
14
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.
15
Julius Center for Health Sciences and Primary Care and Department of Medical Genetics and of Epidemiology, University Medical Center Utrecht, Utrecht, The Netherlands.
16
INSERM U1052, Cancer Research Center of Lyon, Centre Léon Bérard, Lyon, France.
17
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.
18
Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
19
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.
20
Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada, Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada.
21
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health and.
22
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.
23
Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA.
24
Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH, USA.
25
Department of Health Sciences, University of York, York, UK.
26
Ontario Health Study, Toronto, ON, Canada.
27
Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.
28
Department of Epidemiology, MRC-PHE Centre for Environment and Health, School of Public Health and.
29
Department of Biomedical Science and.
30
Department of Epidemiology, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
31
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.
32
Westat, Rockville, MD, USA.
33
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
34
Department of Internal Medicine, Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
35
Departments of Laboratory Medicine and Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
36
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
37
Centre Heni Becquerel, Université de Rouen, Rouen, France.
38
Lymphoid Malignancies Unit, Henri Mondor Hospital and University Paris Est, Créteil, France.
39
Department of Pathology, AP-HP, Necker Enfants malades, Université Paris Descartes, Sorbonne Paris Cité, France.
40
Department of Epidemiology Research, Division of Health Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark.
41
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
42
Department of Epidemiology, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
43
Department of Medical Biosciences, Umeå University, Umeå, Sweden.
44
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
45
Division of Environmental Health Sciences, University of California Berkeley School of Public Health, Berkeley, CA, USA.
46
Department of Preventive Medicine and Norris Comprehensive Cancer Center, USC Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
47
Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, MI, USA.
48
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
49
Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
50
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Baden-Württemberg, Germany.
51
Cancer Epidemiology Research Programme, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain, CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.
52
The Tisch Cancer Institute and.
53
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic.
54
EA 4184, Registre des Hémopathies Malignes de Côte d'Or, University of Burgundy and Dijon University Hospital, Dijon, France.
55
School of Nursing and Human Sciences, Dublin City University, Dublin, Ireland.
56
Icahn Institute for Genomics and Multiscale Biology, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
57
Department of Environmental Health Sciences and.
58
Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
59
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia, Department of Histopathology, Douglass Hanly Moir Pathology, Sydney, NSW, Australia.
60
Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, VIC, Australia.
61
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.
62
Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
63
School of Public Health, Imperial College London, London, UK.
64
MRC-PHE Centre for Environment and Health, School of Public Health and Human Genetics Foundation, Turin, Italy.
65
Department of Epidemiology, German Institute for Human Nutrition, Potsdam, Germany.
66
Danish Cancer Society Research Center, Copenhagen, Denmark.
67
Hematology Unit, Ospedale Oncologico di Riferimento Regionale A. Businco, Cagliari, Italy.
68
Department of Surgery and Translational Medicine, Section of Anatomo-Pathology, University of Florence, Florence, Italy.
69
Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Monserrato, Cagliari, Italy.
70
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.
71
Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
72
Department of Epidemiology.
73
Department of Epidemiology, College of Information Science and Technology, Dalian Maritime University, Dalian, Liaoning Province, China.
74
Department of Health Studies, University of Chicago, Chicago, IL, USA.
75
Department of Statistics, Dongguk University, Seoul, Republic of Korea.
76
Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
77
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.
78
Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
79
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

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.

PMID:
27008888
PMCID:
PMC4854019
DOI:
10.1093/hmg/ddw027
[Indexed for MEDLINE]
Free PMC Article

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