Title: | Association Between Telomere Length And Risk Of Cancer And Non-neoplastic Diseases: A Mendelian Randomization Study |
Author: | Haycock, Philip C. Burgess, Stephen Nounu, Aayah Zheng, Jie Okoli, George N. Bowden, Jack Wade, Kaitlin H. Timpson, Nicholas J. Evans, David M. Willeit, Peter Aviv, Abraham Litchfield, Kevin Thompson, Philip J. Ma, Shwu-Fan Brown, W. Mark Petukhova, Lynn Zeng, Chenjie Paternoster, Lavinia Wolpin, Brian M. Betz, Regina C. Rotter, Jerome I. Lee, Jeffrey E. Svenson, Ulrika Carreras-Torres, Robert McKay, James D. Arking, Dan E. Hillary, Ryan P. Ashar, Foram N. Sotoodehnia, Nona Freedman, Neal D. Johansson, Mattias Li, Yong Aben, Katja K. Low, Siew-Kee Comeau, Mary E. Taylor, Philip R. Kubo, Michiaki Hibberd, Martin Lloyd Fan, Xing Zhang, Xuejun Zhu, Caihong Sangiovanni, John Paul Tumino, Rosario Hunt, Steven O'Mara, Tracy A. Smith, George Davey Ferreira, Manuel A. Law, Matthew H. Noth, Imre Fogh, Isabella Cotch, Mary Frances Jensen, Richard A. Munz, Matthias Eeles, Rosalind A. Hemani, Gibran Gunter, Marc J. Abnet, Christian C. Trichopoulou, Antonia Speliotes, Elizabeth Spurdle, Amanda B. Severi, Gianluca Martin, Nicholas G. Zheng, Wei Iles, Mark M. Shu, Xiao-Ou Yang, Qiong Reis, Andre Kahali, Bratati Uebe, Steffen Garcia Barcelo, Mercè Pooley, Karen A. Stolzenberg-Solomon, Rachael Z. Bown, Matthew J. Kim, Jong-Won Bracci, Paige M. Kiemeney, Lambertus A. L. M. Samani, Nilesh J. Bei, Jin-Xin Zeng, Yi-Xin Wong, Tien Yin Försti, Asta Chen, Wei V. Kurian, Kathreena M. Chen, Bowang Wade, Tracey D. Ellinghaus, David Cha, Pei-Chieng Fang, Shenying Baas, Annette F. Overvad, Kim Nakamura, Yusuke Elmore, James R. Klein, Alison P. Ellis, Hayley Patricia Cox, David G. Delattre, Olivier Bowdler, Lisa M. Mirabeau, Olivier Ollila, Hanna M. Thompson, Deborah J. Skibola, Christine F. Cheng, Ching-Yu Brennan, Paul Soranzo, Nicole Lin, Kuang Telomeres Mendelian Randomization Collaboration Tang, Clara S. Vermeulen, Sita H. Powell, John F. Worrall, Bradford B. Montgomery, Grant W. Morrison, Alanna C. Mangino, Massimo Levy, Daniel Amundadottir, Laufey Kimura, Masayuki Hwang, Shih-Jen Spector, Tim D. Neale, Rachel E. Onland-Moret, N. Charlotte Woo, Daniel Sasaki, Tsukasa Flores, Carlos Fischer, Annegret Rij, Andre Van Rice, Kenneth Relton, Caroline L. Martin, Richard M. Su, Wen-Hui Franke, Andre Barr, Graham Gordon, Scott Yerges-Armstrong, Laura M. Gaunt, Tom R. Chang, Yu-Sun Nyholt, Dale R. Gaborieau, Valérie Markus, Hugh Stephen Hung, Rayjean J. Amos, Christopher I. Manichaikul, Ani W. Otowa, Takeshi Rosand, Jonathan Han, Fang Langefeld, Carl D. Dommisch, Henrik Wang, Feijie Maris, John M. Christiano, Angela M. Lund, Eiliv Duell, Eric J. Canzian, Federico Mijatovic, Vladan Han, Jiali Kawamura, Yoshiya Chang, Kai-Ping Ralston, Stuart H. Hui, Jennie Xie, Gang Foo, Jia Nee Sapkota, Yadav T'hof, Femke N.G. van Schwartz, David A. Tromp, Gerard Fingerlin, Tasha E. Jones, Gregory T. Cho, Michael H. Kuivaniemi, Helena Scelo, Ghislaine Wiencke, John K. Albagha, Omar Schaefer, Arne S. Walsh, Kyle M. Hüffmeier, Ulrike Landi, Stefano Hokanson, John E. Olson, Sara H. Gallinger, Steven Smith, Nicholas L. Li, Donghui Thompson, Susan D. Petersen, Gloria M. Risch, Harvey A. Zondervan, Krina T. Abecasis, Gonçalo R. Heel, David A. van Felix, Janine F. Davila, Sonia Liu, Jianjun Hunt, Karen Lee, Chaeyoung Jonas, Jost B. Silverman, Edwin K. Wrensch, Margaret Rice, Terri Lin, Xu Turnbull, Clare Standl, Marie Siminovitch, Katherine |
Keywords: | Nucleòtids Càncer Nucleotides Cancer |
Issue Date: | 1-May-2017 |
Publisher: | American Medical Association |
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. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1001/jamaoncol.2016.5945 |
It is part of: | Jama Oncology, 2017, vol. 3, num. 5, p. 636-651 |
URI: | http://hdl.handle.net/2445/124398 |
Related resource: | https://doi.org/10.1001/jamaoncol.2016.5945 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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