Article open access publication

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

JAMA Oncology, American Medical Association (AMA), ISSN 2374-2445

Volume 3, 5, 2017

DOI:10.1001/jamaoncol.2016.5945, Dimensions: pub.1084006025, PMC: PMC5638008, PMID: 28241208,

Authors

Evans, David M (1) (3)
Willeit, Peter (2) (4)
Hung, Rayjean J (15) (16)
Severi, Gianluca (27) (28) (29) (30)
Tromp, Gerard (37) (38)
Kuivaniemi, Helena (37) (38)
Han, Jiali (45)
Aben, Katja K H (47) (48)
Turnbull, Clare (9) (49)
Li, Yong (54)
Nyholt, Dale R (11) (59)
Hui, Jennie (66) (67) (68) (69)
Fan, Xing (74)
Rotter, Jerome I (78) (79)
Munz, Matthias (81) (82)
Han, Fang (83)
Albagha, Omar (85) (86)
Zheng, Wei (87)
Otowa, Takeshi (90) (91)
Xie, Gang (15) (16)
Zeng, Yi-Xin (93) (94)
Försti, Asta (26) (95)
Fischer, Annegret (97) (98)
Flores, Carlos (99) (100)
Noth, Imre (101)
Ma, Shwu-Fan (101)
Cox, David G (103)
Su, Wen-Hui (107) (108)
Levy, Daniel (114)
Hunt, Steven (115)
Cheng, Ching-Y U (119) (120) (121) (122)
Jonas, Jost B. (123) (124)
Wong, Tien Yin (119) (120) (121) (122)
Lin, Kuang (125)
Martin, Richard M. (1) (126)

Affiliations

Organisations

  1. (1) University of Bristol, grid.5337.2
  2. (2) University of Cambridge, grid.5335.0
  3. (3) University of Queensland, grid.1003.2
  4. (4) Innsbruck Medical University, grid.5361.1
  5. (5) Rutgers, The State University of New Jersey, grid.430387.b
  6. (6) Guy's and St Thomas' NHS Foundation Trust, grid.420545.2
  7. (7) Department of Twin Research and Genetic Epidemiology, King’s College London, London England
  8. (8) Brain Tumour Research Group, Institute of Clinical Neuroscience, Learning and Research Building, Southmead Hospital, University of Bristol
  9. (9) Institute of Cancer Research, grid.18886.3f
  10. (10) The University of Texas MD Anderson Cancer Center, grid.240145.6
  11. (11) QIMR Berghofer Medical Research Institute, grid.1049.c
  12. (12) University of Leeds, grid.9909.9
  13. (13) Boston University, grid.189504.1
  14. (14) University of Virginia, grid.27755.32
  15. (15) University of Toronto, grid.17063.33
  16. (16) Lunenfeld-Tanenbaum Research Institute, grid.250674.2
  17. (17) Dartmouth College, grid.254880.3
  18. (18) Dana-Farber Cancer Institute, grid.65499.37
  19. (19) National Institutes of Health, grid.94365.3d
  20. (20) National Cancer Institute, grid.48336.3a
  21. (21) Hellenic Health Foundation, grid.424637.0
  22. (22) National and Kapodistrian University of Athens, grid.5216.0
  23. (23) University Medical Center Utrecht, grid.7692.a
  24. (24) The Arctic University of Norway, grid.10919.30
  25. (25) Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Barcelona, Spain
  26. (26) German Cancer Research Center, grid.7497.d
  27. (27) Cancer Council Victoria, grid.3263.4
  28. (28) Centre for research in epidemiology and population health, grid.463845.8
  29. (29) Human Genetics Foundation, grid.428948.b
  30. (30) Institut Gustave Roussy, grid.14925.3b
  31. (31) Aarhus University, grid.7048.b, AU
  32. (32) Imperial College London, grid.7445.2
  33. (33) Cancer Registry, Azienda Ospedaliera “Civile M.P. Arezzo,” Ragusa, Italy
  34. (34) Umeå University, grid.12650.30
  35. (35) University of Otago, grid.29980.3a
  36. (36) Department of Cardiovascular Sciences and the NIHR Leicester, Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, England
  37. (37) Stellenbosch University, grid.11956.3a
  38. (38) Geisinger Health System, grid.280776.c
  39. (39) International Agency For Research On Cancer, grid.17703.32
  40. (40) University of California, San Francisco, grid.266102.1
  41. (41) Memorial Sloan Kettering Cancer Center, grid.51462.34
  42. (42) Mayo Clinic, grid.66875.3a
  43. (43) Yale University, grid.47100.32
  44. (44) Johns Hopkins University, grid.21107.35
  45. (45) Indiana University – Purdue University Indianapolis, grid.257413.6
  46. (46) Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania
  47. (47) Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands
  48. (48) Radboud University Nijmegen Medical Centre, grid.10417.33
  49. (49) Queen Mary University of London, grid.4868.2
  50. (50) Helmholtz Zentrum München, grid.4567.0
  51. (51) University of Michigan, grid.214458.e
  52. (52) Department of Biochemistry and Molecular and Cellular Biology, Georgetown School of Medicine, Washington, DC
  53. (53) National Institute On Alcohol Abuse and Alcoholism, grid.420085.b
  54. (54) University of Freiburg, grid.5963.9
  55. (55) University of Verona, grid.5611.3
  56. (56) RIKEN, grid.7597.c
  57. (57) Nuffield Department of Obstetrics and Gynecology, University of Oxford, John Radcliffe Hospital, Oxford, England
  58. (58) Wellcome Centre for Human Genetics, grid.270683.8
  59. (59) Queensland University of Technology, grid.1024.7
  60. (60) University of Washington, grid.34477.33
  61. (61) University of Cincinnati, grid.24827.3b
  62. (62) Massachusetts General Hospital, grid.32224.35
  63. (63) Wake Forest University, grid.241167.7
  64. (64) Brigham and Women's Hospital, grid.62560.37
  65. (65) University of Colorado Anschutz Medical Campus, grid.430503.1
  66. (66) PathWest Laboratory Medicine of Western Australia, Perth, Australia
  67. (67) School of Population Health, University of WA, Perth, Australia
  68. (68) Sir Charles Gairdner Hospital, grid.3521.5
  69. (69) University of Western Australia, grid.1012.2
  70. (70) The University of Texas Health Science Center at Houston, grid.267308.8
  71. (71) Erasmus University Medical Center, grid.5645.2
  72. (72) Columbia University, grid.21729.3f
  73. (73) University of Bonn, grid.10388.32
  74. (74) First Affiliated Hospital of Anhui Medical University, grid.412679.f
  75. (75) Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
  76. (76) Shanghai Institutes for Biological Sciences, grid.419092.7
  77. (77) Department of Biomedical Research, National Jewish Health Hospital, Denver, Colorado
  78. (78) Harbor–UCLA Medical Center, grid.239844.0
  79. (79) Los Angeles Biomedical Research Institute, grid.279946.7
  80. (80) National Eye Institute, grid.280030.9
  81. (81) University of Lübeck, grid.4562.5
  82. (82) Charité, grid.6363.0
  83. (83) Peking University People's Hospital, grid.411634.5
  84. (84) Lucile Packard Children's Hospital, grid.414123.1
  85. (85) Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha, Qatar
  86. (86) Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland
  87. (87) Vanderbilt University Medical Center, grid.412807.8
  88. (88) University of Erlangen-Nuremberg, grid.5330.5
  89. (89) Shonan Kamakura General Hospital, grid.415816.f
  90. (90) Teikyo Heisei University, grid.440938.2
  91. (91) University of Tokyo, grid.26999.3d
  92. (92) Genome Institute of Singapore, grid.418377.e
  93. (93) Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
  94. (94) Chinese Academy of Medical Sciences & Peking Union Medical College, grid.506261.6
  95. (95) Lund University, grid.4514.4
  96. (96) University of Pisa, grid.5395.a
  97. (97) University Hospital Schleswig-Holstein, grid.412468.d
  98. (98) Kiel University, grid.9764.c
  99. (99) Hospital Universitario Nuestra Señora de Candelaria, grid.411331.5
  100. (100) Institute of Health Carlos III, grid.413448.e
  101. (101) Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Illinois
  102. (102) Samsung Medical Center, grid.414964.a
  103. (103) Cancer Center of Lyon, grid.462282.8
  104. (104) Institute Curie, grid.418596.7
  105. (105) University of Alabama at Birmingham, grid.265892.2
  106. (106) University of Hong Kong, grid.194645.b
  107. (107) Taoyuan Chang Gung Memorial Hospital, grid.454210.6
  108. (108) Chang Gung University, grid.145695.a
  109. (109) Flinders University, grid.1014.4
  110. (110) Soongsil University, grid.263765.3
  111. (111) RIKEN Center for Integrative Medical Science, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan
  112. (112) Kobe University, grid.31432.37
  113. (113) Center for Personalized Therapeutics, The University of Chicago, Chicago, Illinois
  114. (114) National Heart Lung and Blood Institute, grid.279885.9
  115. (115) Department of Genetic Medicine, Weill Cornell Medicine in Qatar, Doha, Qatar
  116. (116) Wellcome Sanger Institute, grid.10306.34
  117. (117) Columbia University Medical Center, grid.239585.0
  118. (118) Department of Medicine, University of Maryland, Baltimore
  119. (119) Duke NUS Graduate Medical School, grid.428397.3
  120. (120) National University Health System, grid.410759.e
  121. (121) National University of Singapore, grid.4280.e
  122. (122) Singapore National Eye Center, grid.419272.b
  123. (123) Capital Medical University, grid.24696.3f
  124. (124) Heidelberg University, grid.7700.0
  125. (125) King's College London, grid.13097.3c
  126. (126) University of Bristol/University Hospitals Bristol NHS Foundation Trust National Institute for Health Research Bristol Nutrition Biomedical Research Unit, Bristol, England

Description

Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015. Study Selection: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Data Extraction and Synthesis: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Main Outcomes and Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Results: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). Conclusions and Relevance: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.

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Aarhus University

Danish Open Access Indicator

2017: Blocked

Research area: Medicine

Danish Bibliometrics Indicator

2017: Level 1

Research area: Medicine

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Times Cited: 169

Field Citation Ratio (FCR): 71.61

Relative Citation ratio (RCR): 13.08

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Green, Published