Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/124398
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
Foo, Jia Nee
Hüffmeier, Ulrike
Liu, Jianjun
Brown, W. Mark
Johansson, Mattias
Kubo, Michiaki
Silverman, Edwin K.
Gunter, Marc
Speliotes, Elizabeth
Kim, Jong-Won
Kiemeney, Lambertus A.
Bei, Jin-Xin
Zeng, Yi-Xin
Wong, Tien Yin
Försti, Asta
Kurian, Kathreena M.
Chen, Bowang
Wade, Tracey D.
Cha, Pei-Chieng
Baas, Annette F.
Nakamura, Yusuke
Elmore, James R.
Klein, Alison P.
Cox, David G.
Delattre, Olivier
Bowdler, Lisa M.
Mirabeau, Olivier
Skibola, Christine F.
Cheng, Ching-Yu
Brennan, Paul
Lin, Kuang
Tang, Clara S.
Vermeulen, Sita H.
Powell, John F.
Montgomery, Grant W.
Morrison, Alanna C.
Levy, Daniel
Amundadottir, Laufey
Kimura, Masayuki
Hwang, Shih-Jen
Lee, Jeffrey E.
Aben, Katja K.
Hunt, Steven
Hemani, Gibran
Yang, Qiong
Fang, Shenying
Ollila, Hanna M.
Worrall, Bradford B.
Sasaki, Tsukasa
Flores, Carlos
Rij, Andre Van
Rice, Kenneth
Relton, Caroline L.
Martin, Richard M.
Franke, Andre
Low, Siew-Kee
Smith, George Davey
Trichopoulou, Antonia
Garcia Barcelo, Mercè
Chen, Wei V.
Telomeres Mendelian Randomization Collaboration
Spector, Tim
Onland-Moret, N. Charlotte
Gaunt, Tom R.
Chang, Yu-Sun
Nyholt, Dale R.
Gaborieau, Valerie
Markus, Hugh Stephen
Hung, Rayjean J.
Amos, Chris I.
Otowa, Takeshi
Ferreira, Manuel A.
Spurdle, Amanda B.
Bown, Matthew J.
Ellinghaus, David
Thompson, Deborah J.
Mangino, Massimo
Samani, Nilesh J.
Su, Wen-Hui
Barr, Graham
Wang, Feijie
Maris, John M.
Christiano, Angela M.
Lund, Eiliv
Duell, Eric J.
Canzian, Federico
Mijatovic, Vladan
Kawamura, Yoshiya
Chang, Kai-Ping
Severi, Gianluca
Bracci, Paige M.
Overvad, Kim
Soranzo, Nicole
Neale, Rachel E.
Fischer, Annegret
Ellis, Hayley Patricia
Manichaikul, Ani W.
Han, Fang
Hui, Jennie
Sapkota, Yadav
T'hof, Femke N.G. van
Schwartz, David A.
Tromp, Gerard
Jones, Gregory T.
Cho, Michael H.
Kuivaniemi, Helena
Wiencke, John K.
Albagha, Omar
Walsh, Kyle M.
Landi, Stefano
Olson, Sara H.
Gallinger, Steven
Smith, Nicholas L.
Li, Donghui
Petersen, Gloria M.
Risch, Harvey A.
Zondervan, Krina T.
Heel, David A. van
Davila, Sonia
Hunt, Karen
Lee, Chaeyoung
Jonas, Jost B.
Wrensch, Margaret
Rice, Terri
Lin, Xu
Turnbull, Clare
Litchfield, Kevin
Thompson, Philip J.
Ma, Shwu-Fan
Petukhova, Lynn
Paternoster, Lavinia
Wolpin, Brian M.
Betz, Regina C.
Svenson, Ulrika
Carreras-Torres, Robert
Arking, Dan E.
Hillary, Ryan P.
Ashar, Foram N.
Sotoodehnia, Nona
Woo, Daniel
Gordon, Scott
Rosand, Jonathan
Han, Jiali
Fingerlin, Tasha
Felix, Janine F.
Standl, Marie
Rotter, Jerome I.
Comeau, Mary E.
Taylor, Philip R.
Hibberd, Martin Lloyd
Fan, Xing
Zhang, Xuejun
Zhu, Caihong
Tumino, Rosario
Yerges-Armstrong, Laura M.
Langefeld, Carl D.
Ralston, Stuart H.
Scelo, Ghislaine
Thompson, Susan D.
Zeng, Chenjie
Freedman, Neal D.
Li, Yong
Law, Matthew H.
Noth, Imre
Fogh, Isabella
Cotch, Mary Frances
Jensen, Richard A.
Munz, Matthias
Eeles, Rosalind A.
Abnet, Christian C.
Dommisch, Henrik
Xie, Gang
Schaefer, Arne S.
Abecasis, Gonçalo R.
Siminovitch, Katherine
Mckay, James
Hokanson, John E.
Sangiovanni, John Paul
O'mara, Tracy A.
Martin, Nicholas G.
Zheng, Wei
Iles, Mark M.
Shu, Xiao-Ou
Reis, Andre
Kahali, Bratati
Uebe, Steffen
Pooley, Karen A.
Stolzenberg-Solomon, Rachael Z.
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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