Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.
Telomeres Mendelian Randomization Collaboration
van Rij, A
van t'Hof, FNG
van Heel, DA
Davey Smith, G
MetadataShow full item record
<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Data sources</h4>Genomewide association studies (GWAS) published up to January 15, 2015.<h4>Study selection</h4>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.<h4>Data extraction and synthesis</h4>Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.<h4>Main outcomes and measures</h4>Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.<h4>Results</h4>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]).<h4>Conclusions and relevance</h4>It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
The Institute of Cancer Research (Grant ID: Unspecified)
Version of record
Telomeres Mendelian Randomization Collaboration
Genetic Predisposition to Disease
Polymorphism, Single Nucleotide
Aged, 80 and over
Genome-Wide Association Study
Mendelian Randomization Analysis
Molecular & Population Genetics
License start date
JAMA oncology, 2017, 3 (5), pp. 636 - 651
Showing items related by title, author, creator and subject.
Karami, S; Han, Y; Pande, M; Cheng, I; Rudd, J; Pierce, BL; Nutter, EL; Schumacher, FR; Kote-Jarai, Z; Lindstrom, S; Witte, JS; Fang, S; Han, J; Kraft, P; Hunter, DJ; Song, F; Hung, RJ; McKay, J; Gruber, SB; Chanock, SJ; Risch, A; Shen, H; Haiman, CA; Boardman, L; Ulrich, CM; Casey, G; Peters, U; Amin Al Olama, A; Berchuck, A; Berndt, SI; Bezieau, S; Brennan, P; Brenner, H; Brinton, L; Caporaso, N; Chan, AT; Chang-Claude, J; Christiani, DC; Cunningham, JM; Easton, D; Eeles, RA; Eisen, T; Gala, M; Gallinger, SJ; Gayther, SA; Goode, EL; Grönberg, H; Henderson, BE; Houlston, R; Joshi, AD; Küry, S; Landi, MT; Le Marchand, L; Muir, K; Newcomb, PA; Permuth-Wey, J; Pharoah, P; Phelan, C; Potter, JD; Ramus, SJ; Risch, H; Schildkraut, J; Slattery, ML; Song, H; Wentzensen, N; White, E; Wiklund, F; Zanke, BW; Sellers, TA; Zheng, W; Chatterjee, N; Amos, CI; Doherty, JA; GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL (2016-12)Telomeres cap chromosome ends, protecting them from degradation, double-strand breaks, and end-to-end fusions. Telomeres are maintained by telomerase, a reverse transcriptase encoded by TERT, and an RNA template encoded ...
Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma. Machiela, MJ; Hofmann, JN; Carreras-Torres, R; Brown, KM; Johansson, M; Wang, Z; Foll, M; Li, P; Rothman, N; Savage, SA; Gaborieau, V; McKay, JD; Ye, Y; Henrion, M; Bruinsma, F; Jordan, S; Severi, G; Hveem, K; Vatten, LJ; Fletcher, T; Koppova, K; Larsson, SC; Wolk, A; Banks, RE; Selby, PJ; Easton, DF; Pharoah, P; Andreotti, G; Freeman, LEB; Koutros, S; Albanes, D; Mannisto, S; Weinstein, S; Clark, PE; Edwards, TE; Lipworth, L; Gapstur, SM; Stevens, VL; Carol, H; Freedman, ML; Pomerantz, MM; Cho, E; Kraft, P; Preston, MA; Wilson, KM; Gaziano, JM; Sesso, HS; Black, A; Freedman, ND; Huang, W-Y; Anema, JG; Kahnoski, RJ; Lane, BR; Noyes, SL; Petillo, D; Colli, LM; Sampson, JN; Besse, C; Blanche, H; Boland, A; Burdette, L; Prokhortchouk, E; Skryabin, KG; Yeager, M; Mijuskovic, M; Ognjanovic, M; Foretova, L; Holcatova, I; Janout, V; Mates, D; Mukeriya, A; Rascu, S; Zaridze, D; Bencko, V; Cybulski, C; Fabianova, E; Jinga, V; Lissowska, J; Lubinski, J; Navratilova, M; Rudnai, P; Szeszenia-Dabrowska, N; Benhamou, S; Cancel-Tassin, G; Cussenot, O; Bueno-de-Mesquita, HB; Canzian, F; Duell, EJ; Ljungberg, B; Sitaram, RT; Peters, U; White, E; Anderson, GL; Johnson, L; Luo, J; Buring, J; Lee, I-M; Chow, W-H; Moore, LE; Wood, C; Eisen, T; Larkin, J; Choueiri, TK; Lathrop, GM; Teh, BT; Deleuze, J-F; Wu, X; Houlston, RS; Brennan, P; Chanock, SJ; Scelo, G; Purdue, MP (2017-11)<h4>Background</h4>Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.<h4>Objective</h4>We ...
Germ line mutations in shelterin complex genes are associated with familial chronic lymphocytic leukemia. Speedy, HE; Kinnersley, B; Chubb, D; Broderick, P; Law, PJ; Litchfield, K; Jayne, S; Dyer, MJS; Dearden, C; Follows, GA; Catovsky, D; Houlston, RS (2016-11)Chronic lymphocytic leukemia (CLL) can be familial; however, thus far no rare germ line disruptive alleles for CLL have been identified. We performed whole-exome sequencing of 66 CLL families, identifying 4 families where ...