Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases

作者：Philip Haycock, Stephen Burgess, Aayah Nounu, Jie Zheng, George N. Okoli, Jack Bowden, Kaitlin H. Wade, Nicholas J. Timpson, David M. Evans, Peter Willeit, Abraham Aviv, Tom R. Gaunt, Gibran Hemani, Massimo Mangino, Hayley Ellis, Kathreena M. Kurian, Karen A. Pooley, Rosalind A. Eeles, Jeffrey E. Lee, Shenying Fang, Wei V. Chen, Matthew H. Law, Lisa Bowdler, Mark M. Iles, Qiong Yang, Bradford B. Worrall, Hugh S. Markus, Rayjean J. Hung, Chris Amos, Amanda B. Spurdle, Deborah J. Thompson, Tracy A. O’Mara, Brian M. Wolpin, Laufey T. Ámundadóttir, Rachael Z. Stolzenberg‐Solomon, Antonia Trichopoulou, N. Charlotte Onland‐Moret, Eiliv Lund, Eric J. Duell, Federico Canzian, Gianluca Severi, Kim Overvad, Marc J. Gunter, ­Rosario ­Tumino, Ulrika Svenson, André van Rij, Annette F. Baas, Matthew J. Bown, Nilesh J. Samani, Femke N.G. van t’Hof, Gerard Tromp, Gregory T. Jones, Helena Kuivaniemi, James R. Elmore, Mattias Johansson, James McKay, Ghislaine Scélo, Robert Carreras‐Torres, Valérie Gaborieau, Paul Brennan, Paige M. Bracci, Rachel Ε. Neale, Sara H. Olson, Steven Gallinger, Donghui Li, Gloria M. Petersen, Harvey A. Risch, Alison P. Klein, Jiali Han, Christian C. Abnet, Neal D. Freedman, Philip R. Taylor, John M. Maris, Katja K.H. Aben, Lambertus A. Kiemeney, Sita H. Vermeulen, John K. Wiencke, Kyle M. Walsh, Margaret Wrensch, Terri Rice, Clare Turnbull, Kevin Litchfield, Lavinia Paternoster, Marie Standl, Gonçalo R. Abecasis, John Paul SanGiovanni, Yong Li, Vladan Mijatovic, Yadav Sapkota, Siew‐Kee Low, Krina T. Zondervan, Grant W. Montgomery, Dale R. Nyholt, David A. van Heel, Karen A. Hunt, Dan E. Arking, Foram N. Ashar, Nona Sotoodehnia, Daniel Woo, Jonathan Rosand, Mary E. Comeau, W. Mark Brown, Edwin K. Silverman, John E. Hokanson, Michael H. Cho, Jennie Hui, Manuel A. R. Ferreira, Philip J. Thompson, Alanna C. Morrison, Janine F. Felix, Nicholas L. Smith, Angela M. Christiano, Lynn Petukhova, Regina C. Betz, Xing Fan, Xuejun Zhang, Caihong Zhu, Carl D. Langefeld, Susan D. Thompson, Feijie Wang, Lin Xu, David A. Schwartz, Tasha E. Fingerlin, Jerome I. Rotter, Mary Frances Cotch, Richard A. Jensen, Matthias Munz, Henrik Dommisch, Arne S. Schäefer, Fang Han, Hanna M. Ollila, Ryan P. Hillary, Omar Albagha, Stuart H. Ralston, Chenjie Zeng, Wei Zheng, Xiao-Ou Shu, André Reis, Steffen Uebe, Ulrike Hüffmeier, Yoshiya Kawamura, Takeshi Otowa, Tsukasa Sasaki, Martin L. Hibberd, Sonia Dávila, Gang Xie, Katherine A. Siminovitch, Jin‐Xin Bei, Yi‐Xin Zeng, Asta Försti, Bowang Chen, Stefano Landi, Andre Franke, Annegret Fischer, David Ellinghaus, Carlos Flores, Imre Noth, Shwu‐Fan Ma, Jia Nee Foo, Jianjun Liu, Jong‐Won Kim, David G. Cox, Olivier Delattre, Olivier Mirabeau, Christine F. Skibola, Clara Sze-Man Tang, Mercè Garcia-Barceló, Kai‐Ping Chang, Wen-Hui Su, Yu‐Sun Chang, Nicholas G. Martin, Scott D. Gordon, Tracey Wade, Chaeyoung Lee, Michiaki Kubo, Pei-Chieng Cha, Yusuke Nakamura, Daniel Levy, Masayuki Kimura, Shih‐Jen Hwang, S. E. Hunt, Tim D. Spector, Nicole Soranzo, Ani Manichaikul, R. Graham Barr, Bratati Kahali, Elizabeth K. Speliotes, Laura M. Yerges-Armstrong, Ching‐Yu Cheng, Jost B. Jonas, Tien Yin Wong, Isabella Fogh, Kuang Lin, John Powell, Kenneth Rice, Caroline L. Relton, Richard M. Martin, George Davey Smith · 发表于：JAMA Oncology · 年份：2017 · DOI：10.1001/jamaoncol.2016.5945 · 被引用次数：537 · 研究领域：Telomeres, Telomerase, and Senescence、Epigenetics and DNA Methylation、Circadian rhythm and melatonin

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 can...