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