domingo, 12 de marzo de 2017

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. - PubMed - NCBI

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. - PubMed - NCBI



 2017 Feb 23. doi: 10.1001/jamaoncol.2016.5945. [Epub ahead of print]

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.

Telomeres Mendelian Randomization CollaborationHaycock PC1Burgess S2Nounu A1Zheng J1Okoli GN3Bowden J1Wade KH1Timpson NJ1Evans DM4Willeit P5Aviv A6Gaunt TR1Hemani G1Mangino M7Ellis HP8Kurian KM8Pooley KA9Eeles RA10Lee JE11Fang S11Chen WV12Law MH13Bowdler LM14Iles MM15Yang Q16Worrall BB17Markus HS18Hung RJ19Amos CI20Spurdle AB21Thompson DJ9O'Mara TA21Wolpin B22Amundadottir L23Stolzenberg-Solomon R24Trichopoulou A25Onland-Moret NC26Lund E27Duell EJ28Canzian F29Severi G30Overvad K31Gunter MJ32Tumino R33Svenson U34van Rij A35Baas AF36Bown MJ37Samani NJ37van t'Hof FN38Tromp G39Jones GT35Kuivaniemi H39Elmore JR40Johansson M41Mckay J42Scelo G41Carreras-Torres R41Gaborieau V41Brennan P41Bracci PM43Neale RE14Olson SH44Gallinger S45Li D46Petersen GM47Risch HA48Klein AP49Han J50Abnet CC51Freedman ND51Taylor PR51Maris JM52Aben KK53Kiemeney LA54Vermeulen SH54Wiencke JK55Walsh KM55Wrensch M55Rice T56Turnbull C57Litchfield K58Paternoster L1Standl M59Abecasis GR60SanGiovanni JP61Li Y62Mijatovic V63Sapkota Y14Low SK64Zondervan KT65Montgomery GW14Nyholt DR66van Heel DA67Hunt K67Arking DE68Ashar FN68Sotoodehnia N69Woo D70Rosand J71Comeau ME72Brown WM72Silverman EK73Hokanson JE74Cho MH73Hui J75Ferreira MA14Thompson PJ76Morrison AC77Felix JF78Smith NL79Christiano AM80Petukhova L81Betz RC82Fan X83Zhang X83Zhu C83Langefeld CD72Thompson SD84Wang F85Lin X85Schwartz DA86Fingerlin T87Rotter JI88Cotch MF89Jensen RA90Munz M91Dommisch H92Schaefer AS92Han F93Ollila HM94Hillary RP94Albagha O95Ralston SH96Zeng C97Zheng W97Shu XO97Reis A98Uebe S98Hüffmeier U98Kawamura Y99Otowa T100Sasaki T101Hibberd ML102Davila S103Xie G104Siminovitch K104Bei JX105Zeng YX106Försti A107Chen B108Landi S109Franke A110Fischer A111Ellinghaus D112Flores C113Noth I114Ma SF114Foo JN115Liu J115Kim JW116Cox DG117Delattre O118Mirabeau O118Skibola CF119Tang CS120Garcia-Barcelo M120Chang KP121Su WH122Chang YS123Martin NG14Gordon S14Wade TD124Lee C125Kubo M126Cha PC127Nakamura Y128Levy D129Kimura M6Hwang SJ129Hunt S130Spector T131Soranzo N132Manichaikul AW133Barr RG134Kahali B135Speliotes E135Yerges-Armstrong LM136Cheng CY137Jonas JB138Wong TY137Fogh I139Lin K139Powell JF139Rice K140Relton CL1Martin RM141Davey Smith G1.

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.

PMID:
 
28241208
 
DOI:
 
10.1001/jamaoncol.2016.5945

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