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

Journal article


Publication Details

Author(s): Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, Bowden J, Wade KH, Timpson NJ, Evans DM, Willeit P, Aviv A, Gaunt T, Hemani G, Mangino M, Ellis HP, Kurian KM, Pooley KA, Eeles RA, Lee JE, Fang S, Chen WV, Law MH, Bowdler LM, Iles MM, Yang Q, Worrall BB, Markus HS, Hung RJ, Amos CI, Spurdle AB, Thompson DJ, O'Mara TA, Wolpin B, Amundadottir L, Stolzenberg-Solomon R, Trichopoulou A, Onland-Moret C, Lund E, Duell EJ, Canzian F, Severi G, Overvad K, Gunter MJ, Tumino R, Svenson U, Van Rij A, Baas AF, Bown MJ, Samani NJ, Van T'Hof FNG, Tromp G, Jones GT, Kuivaniemi H, Elmore JR, Johansson M, Mckay J, Scelo G, Carreras-Torres R, Gaborieau V, Brennan P, Bracci PM, Neale RE, Olson SH, Gallinger S, Li D, Petersen GM, Risch HA, Klein AP, Han J, Abnet CC, Freedman ND, Taylor PR, Maris JM, Aben KK, Kiemeney LA, Vermeulen SH, Wiencke JK, Walsh KM, Wrensch M, Rice T, Turnbull C, Litchfield K, Paternoster L, Standl M, Abecasis GR, Sangiovanni JP, Li Y, Mijatovic V, Sapkota Y, Low SK, Zondervan KT, Montgomery GW, Nyholt DR, Van Heel DA, Hunt K, Arking DE, Ashar FN, Sotoodehnia N, Woo D, Rosand J, Comeau ME, Brown WM, Silverman EK, Hokanson JE, Cho MH, Hui J, Ferreira MA, Thompson PJ, Morrison AC, Felix JF, Smith NL, Christiano AM, Petukhova L, Betz RC, Fan X, Zhang X, Zhu C, Langefeld CD, Thompson SD, Wang F, Lin X, Schwartz DA, Fingerlin T, Rotter JI, Cotch MF, Jensen RA, Munz M, Dommisch H, Schaefer AS, Han F, Ollila HM, Hillary RP, Albagha O, Ralston SH, Zeng C, Zheng W, Shu XO, Reis A, Uebe S, Hüffmeier U, Kawamura Y, Otowa T, Sasaki T, Hibberd ML, Davila S, Xie G, Siminovitch K, Bei JX, Zeng YX, Foersti A, Chen B, Landi S, Franke A, Fischer A, Ellinghaus D, Flores C, Noth I, Ma SF, Foo JN, Liu J, Kim JW, Cox DG, Delattre O, Mirabeau O, Skibola CF, Tang CS, Garcia-Barcelo M, Chang KP, Su WH, Chang YS, Martin NG, Gordon S, Wade TD, Lee C, Kubo M, Cha PC, Nakamura Y, Levy D, Kimura M, Hwang SJ, Hunt S, Spector T, Soranzo N, Manichaikul A, Barr G, Kahali B, Speliotes E, Yerges-Armstrong L, Cheng CY, Jonas JB, Wong TY, Fogh I, Lin K, Powell JF, Rice K, Relton CL, Martin RM, Smith GD
Journal: JAMA Oncology
Publication year: 2017
Volume: 3
Journal issue: 5
Pages range: 636-651
ISSN: 2374-2437
eISSN: 2374-2445


Abstract


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.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.Genomewide association studies (GWAS) published up to January 15, 2015.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.Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.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]).It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.



FAU Authors / FAU Editors

Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut


External institutions with authors

Aarhus University
Agency for Science, Technology and Research (A*STAR)
Albert-Ludwigs-Universität Freiburg
Anhui Medical University
Azienda Ospedaliera Civile M. P.Arezzo
Brigham and Women's Hospital (BWH)
Capital University of Medical Sciences / 首都医科大学
Catalan Institute of Oncology / Institut Català d'Oncologia (ICO)
Chang Gung University (CGU) / 長庚大學
Charité - Universitätsmedizin Berlin
Christian-Albrechts-Universität zu Kiel
Columbia University
Dana–Farber Cancer Institute
Dartmouth College
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center (MC)
Flinders University
Framingham Heart Study
Geisinger Health System
Genome Institute of Singapore
Hamad Bin Khalifa University
Harbor–UCLA Medical Center
Harvard University
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU)
Imperial College London / The Imperial College of Science, Technology and Medicine
Indiana University
International Agency for Research on Cancer (IARC)
Johns Hopkins University
King’s College London
Kobe University / 神戸大学
Massachusetts General Hospital
Mayo Clinic
Memorial Sloan Kettering Cancer Center
Mount Sinai Hospital (MSH)
National and Kapodistrian University of Athens
National Cancer Institute (NCI)
National Eye Institute
National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Jewish Health
Peking University (PKU) / 北京大学
PSL Research University / Université de recherche Paris Sciences et Lettres
QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research)
Queen Mary, University of London
Radboud University Nijmegen
Rheinische Friedrich-Wilhelms-Universität Bonn
Riken / 理研
Shonan Kamakura General Hospital
Singapore National Eye Centre (SNEC)
Sir Charles Gairdner Hospital
Soongsil University
Stanford University
Sungkyunkwan University (SKKU)
Sun Yat-Sen University
Taoyuan Chang Gung Memorial Hospital
The Institute of Cancer Research (ICR)
The State University of New Jersey (Rutgers)
Umeå University
Universidad de La Laguna
Universitätsklinikum Heidelberg
Universitätsklinikum Schleswig-Holstein (UKSH)
University Medical Centre Utrecht (UMC Utrecht)
University of Alabama at Birmingham (UAB)
University of Bristol
University of California San Francisco (UCSF)
University of Cambridge
University of Chicago
University of Chinese Academy of Sciences
University of Cincinnati
University of Colorado System
University of Edinburgh
University of Hong Kong (HKU) / 香港大學
University of Leeds
University of Leicester
University of Michigan
University of Otago
University of Oxford
University of Paris 11 - Paris-Sud / Université Paris XI Paris-Sud
University of Pennsylvania
University of Pisa / Università di Pisa (UniPi)
University of Stellenbosch / Universiteit van Stellenbosch
University of Texas Health Science Center at Houston (UTHealth)
University of Texas MD Anderson Cancer Center
University of Tokyo
University of Tromsø
University of Verona / Università degli Studi di Verona
University of Virginia (UVA)
University of Washington
University of Western Australia (UWA)
Vanderbilt University
Wake Forest University
Weill Cornell Medicine-Qatar (WCM-Q)
Wellcome Trust Sanger Institute - Genome Research Limited


How to cite

APA:
Haycock, P.C., Burgess, S., Nounu, A., Zheng, J., Okoli, G.N., Bowden, J.,... Smith, G.D. (2017). Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. JAMA Oncology, 3(5), 636-651. https://dx.doi.org/10.1001/jamaoncol.2016.5945

MLA:
Haycock, Philip C., et al. "Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study." JAMA Oncology 3.5 (2017): 636-651.

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Last updated on 2019-13-01 at 07:09