@article{3174964,
    title = "Association Between Telomere Length and Risk of Cancer and
Non-Neoplastic Diseases A Mendelian Randomization Study",
    author = "Haycock, Philip C. and Burgess, Stephen and Nounu, Aayah and Zheng, Jie and and Okoli, George N. and Bowden, Jack and Wade, Kaitlin Hazel and and Timpson, Nicholas J. and Evans, David M. and Willeit, Peter and Aviv, and Abraham and Gaunt, Tomr. and Hemani, Gibran and Mangino, Massimo and and Ellis, Hayley Patricia and Kurian, Kathreena M. and Pooley, Karen A. and and Eeles, Rosalind A. and Lee, Jeffrey E. and Fang, Shenying and Chen, Wei and V. and Law, Matthew H. and Bowdler, Lisa M. and Iles, Mark M. and Yang, and Qiong and Worrall, Bradford B. and Markus, Hugh Stephen and Hung, and Rayjean J. and Amos, Chris I. and Spurdle, Amanda B. and Thompson, and Deborah J. and O'Mara, Tracy A. and Wolpin, Brian and Amundadottir, and Laufey and Stolzenberg-Solomon, Rachael and Trichopoulou, Antonia and and Onland-Moret, Charlotte and Lund, Eiliv and Duell, Eric J. and Canzian, and Federico and Severi, Gianluca and Overvad, Kim and Gunter, Marc J. and and Tumino, Rosario and Svenson, Ulrika and van Rij, Andre and Baas, Annette and F. and Bown, Matthew J. and Samani, Nilesh J. and van t'Hof, Femke N. G. and and Tromp, Gerard and Jones, Gregory T. and Kuivaniemi, Helena and and Elmore, James R. and Johansson, Mattias and Mckay, James and Scelo, and Ghislaine and carreras-Torres, Robert and Gaborieau, Valerie and and Brennan, Paul and Bracci, Paige M. and Neale, Rachel E. and Olson, Sara and H. and Gallinger, Steven and Li, Donghui and Petersen, Gloria M. and and Risch, Harvey A. and Klein, Alison P. and Han, Jiali and Abnet, and Christian C. and Freedman, Neal D. and Taylor, Philip R. and Maris, John and M. and Aben, Katja K. and Kiemeney, Lambertus A. and Vermeulen, Sita H. and and Wiencke, John K. and Walsh, Kyle M. and Wrensch, Margaret and Rice, and Terri and Turnbull, Clare and Litchfield, Kevin and Paternoster, Lavinia and and Standl, Marie and Abecasis, Goncalo R. and SanGiovanni, John Paul and and Li, Yong and Mijatovic, Vladan and Sapkota, Yadav and Low, Siew-Kee and and Zondervan, Krina T. and Montgomery, Grant W. and Nyholt, Dale R. and and van Heel, David A. and Hunt, Karen and Arking, Dan E. and Ashar, Foram and N. and Sotoodehnia, Nona and Woo, Daniel and Rosand, Jonathan and and Comeau, Mary E. and Brown, W. Mark and Silverman, Edwin K. and Hokanson, and John E. and Cho, Michael H. and Hui, Jennie and Ferreira, Manuel A. and and Thompson, Philip J. and Morrison, Alanna C. and Felix, Janine F. and and Smith, Nicholas L. and Christiano, Angela M. and Petukhova, Lynn and and Betz, Regina C. and Fan, Xing and Zhang, Xuejun and Zhu, Caihong and and Langefeld, Carl D. and Thompson, Susan D. and Wang, Feijie and Lin, Xu and and Schwartz, David A. and Fingerlin, Tasha and Rotter, Jerome I. and and Cotch, Mary Frances and Jensen, Richard A. and Munz, Matthias and and Dommisch, Henrik and Schaefer, Arne S. and Han, Fang and Ollila, Hanna and M. and Hillary, Ryan P. and Albagha, Omar and Ralston, Stuart H. and and Zeng, Chenjie and Zheng, Wei and Shu, Xiao-Ou and Reis, Andre and Uebe, and Steffen and Hueffmeier, Ulrike and Kawamura, Yoshiya and Otowa, Takeshi and and Sasaki, Tsukasa and Hibberd, Martin Lloyd and Davila, Sonia and Xie, and Gang and Siminovitch, Katherine and Bei, Jin-Xin and Zeng, Yi-Xin and and Foersti, Asta and Chen, Bowang and Landi, Stefano and Franke, Andre and and Fischer, Annegret and Ellinghaus, David and Flores, Carlos and Noth, and Imre and Ma, Shwu-Fan and Foo, Jia Nee and Liu, Jianjun and Kim, and Jong-Won and Cox, David G. and Delattre, Olivier and Mirabeau, Olivier and and Skibola, Christine F. and Tang, Clara S. and Garcia-Barcelo, Merce and and Chang, Kai-Ping and Su, Wen-Hui and Chang, Yu-Sun and Martin, and Nicholas G. and Gordon, Scott and Wade, Tracey D. and Lee, Chaeyoung and and Kubo, Michiaki and Cha, Pei-Chieng and Nakamura, Yusuke and Levy, Daniel and and Kimura, Masayuki and Hwang, Shih-Jen and Hunt, Steven and Spector, and Tim and Soranzo, Nicole and Manichaikul, Aniw. and Barr, Graham and and Kahali, Bratati and Speliotes, Elizabeth and Yerges-Armstrong, LauraM. and and Cheng, Ching-Yu and Jonas, Jost B. and Wong, Tien Yin and Fogh, and Isabella and Lin, Kuang and Powell, John F. and Rice, Kenneth and and Relton, Caroline L. and Martin, Richard M. and Smith, George Davey and and Telomeres Mendelian Randomization",
    journal = "JAMA Oncology",
    year = "2017",
    volume = "3",
    number = "5",
    pages = "636-651",
    publisher = "AMER MEDICAL ASSOC",
    issn = "2374-2437, 2374-2445",
    doi = "10.1001/jamaoncol.2016.5945",
    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."
}