lunes, 6 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 PCBurgess SNounu AZheng JOkoli GNBowden JWade KHTimpson NJEvans DMWilleit PAviv AGaunt TRHemani GMangino MEllis HPKurian KMPooley KAEeles RALee JEFang SChen WVLaw MHBowdler LMIles MMYang QWorrall BBMarkus HSHung RJAmos CISpurdle ABThompson DJO'Mara TAWolpin BAmundadottir LStolzenberg-Solomon RTrichopoulou AOnland-Moret NCLund EDuell EJCanzian FSeveri GOvervad KGunter MJTumino RSvenson Uvan Rij ABaas AFBown MJSamani NJvan t'Hof FNTromp GJones GTKuivaniemi HElmore JRJohansson MMckay JScelo GCarreras-Torres RGaborieau VBrennan PBracci PMNeale REOlson SHGallinger SLi DPetersen GMRisch HAKlein APHan JAbnet CCFreedman NDTaylor PRMaris JMAben KKKiemeney LAVermeulen SHWiencke JKWalsh KMWrensch MRice TTurnbull CLitchfield KPaternoster LStandl MAbecasis GRSanGiovanni JPLi YMijatovic VSapkota YLow SKZondervan KTMontgomery GWNyholt DRvan Heel DAHunt KArking DEAshar FNSotoodehnia NWoo DRosand JComeau MEBrown WMSilverman EKHokanson JECho MHHui JFerreira MAThompson PJMorrison ACFelix JFSmith NLChristiano AMPetukhova LBetz RCFan XZhang XZhu CLangefeld CDThompson SDWang FLin XSchwartz DAFingerlin TRotter JICotch MFJensen RAMunz MDommisch HSchaefer ASHan FOllila HMHillary RPAlbagha ORalston SHZeng CZheng WShu XOReis AUebe SHüffmeier UKawamura YOtowa TSasaki THibberd MLDavila SXie GSiminovitch KBei JXZeng YXFörsti AChen BLandi SFranke AFischer AEllinghaus DFlores CNoth IMa SFFoo JNLiu JKim JWCox DGDelattre OMirabeau OSkibola CFTang CSGarcia-Barcelo MChang KPSu WHChang YSMartin NGGordon SWade TDLee CKubo MCha PCNakamura YLevy DKimura MHwang SJHunt SSpector TSoranzo NManichaikul AWBarr RGKahali BSpeliotes EYerges-Armstrong LMCheng CYJonas JBWong TYFogh ILin KPowell JFRice KRelton CLMartin RMDavey Smith G.



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.


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.


Genomewide association studies (GWAS) published up to January 15, 2015.


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.


Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.


Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.


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]).


It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.


[PubMed - as supplied by publisher]

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