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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.
Haycock, Philip C; Burgess, Stephen; Nounu, Aayah; Zheng, Jie; Okoli, George N; Bowden, Jack; Wade, Kaitlin Hazel; Timpson, Nicholas J; Evans, David M; Willeit, Peter; Aviv, Abraham; Gaunt, Tom R; Hemani, Gibran; Mangino, Massimo; Ellis, Hayley Patricia; Kurian, Kathreena M; Pooley, Karen A; Eeles, Rosalind A; Lee, Jeffrey E; Fang, Shenying; Chen, Wei V; Law, Matthew H; Bowdler, Lisa M; Iles, Mark M; Yang, Qiong; Worrall, Bradford B; Markus, Hugh Stephen; Hung, Rayjean J; Amos, Chris I; Spurdle, Amanda B; Thompson, Deborah J; O'Mara, Tracy A; Wolpin, Brian; Amundadottir, Laufey; Stolzenberg-Solomon, Rachael; Trichopoulou, Antonia; Onland-Moret, N Charlotte; Lund, Eiliv; Duell, Eric J; Canzian, Federico; Severi, Gianluca; Overvad, Kim; Gunter, Marc J; Tumino, Rosario; Svenson, Ulrika; van Rij, Andre; Baas, Annette F; Bown, Matthew J; Samani, Nilesh J; van t'Hof, Femke N G.
Affiliation
  • Haycock PC; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Burgess S; Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.
  • Nounu A; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Zheng J; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Okoli GN; School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Bowden J; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Wade KH; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Timpson NJ; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Evans DM; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England4University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
  • Willeit P; Department of Public Health and Primary Care, University of Cambridge, Cambridge, England5Department of Neurology, Innsbruck Medical University, Austria.
  • Aviv A; Center of Human Development and Aging, Department of Pediatrics, New Jersey Medical School, Rutgers, The State University of New Jersey.
  • Gaunt TR; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Hemani G; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
  • Mangino M; Department of Twin Research and Genetic Epidemiology, King's College London, London England8NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, England.
  • Ellis HP; Brain Tumour Research Group, Institute of Clinical Neuroscience, Learning and Research Building, Southmead Hospital, University of Bristol.
  • Kurian KM; Brain Tumour Research Group, Institute of Clinical Neuroscience, Learning and Research Building, Southmead Hospital, University of Bristol.
  • Pooley KA; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.
  • Eeles RA; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, England.
  • Lee JE; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
  • Fang S; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
  • Chen WV; Department of Clinical Applications & Support, The University of Texas MD Anderson Cancer Center, Houston.
  • Law MH; Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Bowdler LM; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Iles MM; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, England.
  • Yang Q; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
  • Worrall BB; Departments of Neurology and Public Health Sciences, University of Virginia Charlottesville, Virginia.
  • Markus HS; Department of Clinical Neurosciences, University of Cambridge, England.
  • Hung RJ; Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada21Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
  • Amos CI; Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
  • Spurdle AB; Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Thompson DJ; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.
  • O'Mara TA; Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Wolpin B; Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Amundadottir L; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
  • Stolzenberg-Solomon R; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.
  • Trichopoulou A; Hellenic Health Foundation, Athens, Greece28WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
  • Onland-Moret NC; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
  • Lund E; Institute of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway.
  • Duell EJ; 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.
  • Canzian F; Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Severi G; Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France34Institut Gustave Roussy, Villejuif, France35Human Genetics Foundation (HuGeF), Torino, Italy36Cancer Council Victoria and University of Melbourne, Melbourne, Australia.
  • Overvad K; Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
  • Gunter MJ; School of Public Health, Imperial College London, London, England.
  • Tumino R; Cancer Registry, Azienda Ospedaliera "Civile M.P. Arezzo," Ragusa, Italy.
  • Svenson U; Department of Medical Biosciences, Umea University, Umea, Sweden.
  • van Rij A; Surgery Department, University of Otago, Dunedin, New Zealand.
  • Baas AF; Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
  • Bown MJ; Department of Cardiovascular Sciences and the NIHR Leicester, Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, England.
  • Samani NJ; Department of Cardiovascular Sciences and the NIHR Leicester, Cardiovascular Biomedical Research Unit, University of Leicester, Glenfield Hospital, Leicester, England.
  • van t'Hof FNG; Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands.
JAMA Oncol ; 3(5): 636-651, 2017 May 01.
Article in En | MEDLINE | ID: mdl-28241208
ABSTRACT
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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Full text: 1 Database: MEDLINE Main subject: Genetic Predisposition to Disease / Mendelian Randomization Analysis / Telomere Homeostasis / Neoplasms Type of study: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Year: 2017 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Genetic Predisposition to Disease / Mendelian Randomization Analysis / Telomere Homeostasis / Neoplasms Type of study: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Year: 2017 Type: Article