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

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机构: [1]Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England; [2]Univ Bristol, Sch Social & Community Med, Bristol, Avon, England; [3]Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England; [4]Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia; [5]Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria; [6]Rutgers State Univ, New Jersey Med Sch, Dept Pediat, Ctr Human Dev & Aging, Newark, NJ USA; [7]Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England; [8]Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London, England; [9]Univ Bristol, Southmead Hosp, Inst Clin Neurosci Learning & Res Bldg, Brain Tumour Res Grp, Bristol, Avon, England; [10]Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England; [11]Inst Canc Res, London, England; [12]Royal Marsden NHS Fdn Trust, London, England; [13]Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA; [14]Univ Texas MD Anderson Canc Ctr, Dept Clin Applicat & Support, Houston, TX 77030 USA; [15]QIMR Berghofer Med Res Inst, Stat Genet, Brisbane, Qld, Australia; [16]QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia; [17]Univ Leeds, Leeds Inst Canc & Pathol, Sect Epidemiol & Biostat, Leeds, W Yorkshire, England; [18]Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA; [19]Univ Virginia, Dept Neurol, Charlottesville, VA USA; [20]Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA; [21]Univ Cambridge, Dept Clin Neurosci, Cambridge, England; [22]Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada; [23]Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada; [24]Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA; [25]QIMR Berghofer Med Res Inst, Genet & Computat Biol Div, Brisbane, Qld, Australia; [26]Dana Farber Canc Inst, Boston, MA 02115 USA; [27]NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA; [28]NCI, Metab Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA; [29]Hellen Hlth Fdn, Athens, Greece; [30]Univ Athens, Sch Med, Dept Hyg Epidemiol & Med Stat, WHO Collaborating Ctr Nutr & Hlth,Unit Nutr Epide, Athens, Greece; [31]Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands; [32]UiT, Inst Community Med, Tromso, Norway; [33]Catalan Inst Oncol ICO, Bellvitge Biomed Res Inst IDIBELL, Canc Epidemiol Res Program, Unit Nutr & Canc, Barcelona, Spain; [34]German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany; [35]Univ Paris Sud, Univ Paris Saclay, CESP, UVSQ,INSERM, Villejuif, France; [36]Inst Gustave Roussy, Villejuif, France; [37]Human Genet Fdn HuGeF, Turin, Italy; [38]Canc Council Victoria, Melbourne, Vic, Australia; [39]Univ Melbourne, Melbourne, Vic, Australia; [40]Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, Aarhus, Denmark; [41]Imperial Coll London, Sch Publ Hlth, London, England; [42]Azienda Osped Civile MP Arezzo, Canc Registry, Ragusa, Italy; [43]Umea Univ, Dept Med Biosci, Umea, Sweden; [44]Univ Otago, Dept Surg, Dunedin, New Zealand; 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[58]Yale Sch Med, Yale Sch Publ Hlth, New Haven, CT USA; [59]Yale Canc Ctr, New Haven, CT USA; [60]Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA; [61]Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA; [62]Johns Hopkins Sch Med, Dept Epidemiol, Baltimore, MD USA; [63]Indiana Univ, Dept Epidemiol, Fairbanks Sch Publ Hlth, Indianapolis, IN 46204 USA; [64]Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA; [65]NCI, Div Canc Epidemiol & Genet, Rockville, MD USA; [66]Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Philadelphia, PA 19104 USA; [67]Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands; [68]Netherlands Comprehens Canc Org, Utrecht, Netherlands; [69]Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA; [70]Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA; [71]Queen Mary Univ, William Harvey Res Inst, London, England; [72]Inst Canc Res, Div Genet & Epidemiol, London, England; [73]Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany; [74]Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA; [75]NIAAA, Lab Membrane Biophys & Biochem, Sect Nutrit Neurosci, Bethesda, MD USA; [76]Georgetown Sch Med, Dept Biochem & Mol & Cellular Biol, Washington, DC USA; [77]Univ Freiburg, Fac Med, Inst Med Biometry & Stat, Div Genet Epidemiol, Freiburg, Germany; [78]Univ Freiburg, Med Ctr, Freiburg, Germany; [79]Univ Verona, Dept Life & Reprod Sci, Verona, Italy; [80]RIKEN, Inst Phys & Chem Res, Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan; [81]Univ Oxford, Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England; [82]Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynecol, Oxford, England; [83]Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia; [84]Queen Mary Univ London, Blizard Inst, Barts & London Sch Med & Dent, London E1 2AT, England; [85]Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA; [86]Univ Washington, Div Cardiol, Seattle, WA 98195 USA; [87]Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA; [88]Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA; [89]Massachusetts Gen Hosp, Neurol, Ctr Human Genet Res, Boston, MA 02114 USA; [90]Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Ctr Publ Hlth Gen, Winston Salem, NC USA; [91]Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA; [92]Univ Colorado, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA; [93]Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst Inc, Perth, WA, Australia; [94]PathWest Lab Med Western Australia, Perth, WA, Australia; [95]Univ Western Australia, Sch Pathol & Lab Med, Perth, WA, Australia; [96]Univ WA, Sch Populat Hlth, Perth, WA, Australia; [97]Univ Western Australia, Lung Hlth Clin & Inst Resp Hlth, Perth, WA, Australia; [98]Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA; [99]Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands; [100]Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA; [101]Columbia Univ, Dept Dermatol, New York, NY 10027 USA; [102]Columbia Univ, Dept Genet & Dev, New York, NY USA; [103]Columbia Univ, Dept Dermatol, New York, NY 10027 USA; [104]Columbia Univ, Dept Epidemiol, New York, NY USA; [105]Univ Bonn, Inst Human Genet, Bonn, Germany; [106]Anhui Med Univ, Affiliated Hosp 1, Inst Dermatol, Hefei, Anhui, Peoples R China; [107]Anhui Med Univ, Affiliated Hosp 1, Dept Dermatol, Hefei, Anhui, Peoples R China; [108]Univ Cincinnati, Coll Med, Dept Pediat, Ctr Autoimmune Genom & Etiol,Cincinnati Childrens, Cincinnati, OH USA; [109]Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai, Peoples R China; [110]Univ Colorado, Sch Med, Dept Med, Aurora, CO USA; [111]Natl Jewish Hlth Hosp, Dept Biomed Res, Denver, CO USA; [112]Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA; [113]Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA; [114]Harbor UCLA Med Ctr, Dept Med, Torrance, CA 90509 USA; [115]NEI, Epidemiol Branch, Div Epidemiol & Clin Applicat, Intramural Res Program,NIH, Bethesda, MD 20892 USA; [116]Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA; [117]Univ Washington, Dept Med, Seattle, WA USA; [118]Charite Univ Med Berlin, Ctr Dent & Craniofacial Sci, Dept Periodontol & Synopt Dent, Berlin, Germany; [119]Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany; [120]Peking Univ, Peoples Hosp, Dept Pulm Med, Beijing, Peoples R China; [121]Stanford Univ, Ctr Sleep Sci, Palo Alto, CA 94304 USA; [122]Hamad Bin Khalifa Univ, Qatar Biomed Res Inst, Doha, Qatar; [123]Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland; [124]Vanderbilt Univ, Med Ctr, Dept Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN USA; [125]Friedrich Alexander Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany; [126]Shonan Kamakura Gen Hosp, Dept Psychiat, Kanagawa, Japan; [127]Univ Tokyo, Grad Sch Med, Dept Neuropsychiat, Tokyo, Japan; [128]Teikyo Heisei Univ, Major Profess Clin Psychol, Grad Sch Clin Psychol, Tokyo, Japan; [129]Univ Tokyo, Grad Sch Educ, Dept Phys & Hlth Educ, Tokyo, Japan; [130]Genome Inst Singapore, Infect Dis, Singapore, Singapore; [131]Genome Inst Singapore, Human Genet, Singapore, Singapore; [132]Univ Toronto, Dept Med, Toronto, ON, Canada; [133]Univ Toronto, Dept Immunol, Toronto, ON, Canada; [134]Univ Toronto, Dept Mol, Toronto, ON, Canada; [135]Univ Toronto, Dept Genet, Toronto, ON, Canada; [136]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou, Guangdong, Peoples R China; [137]German Canc Res Ctr, Mol Genet Epidemiol, Heidelberg, Germany; [138]Lund Univ, Clin Res Ctr, Ctr Primary Hlth Care Res, Malmo, Sweden; [139]Univ Pisa, Dept Biol, Pisa, Italy; [140]Univ Hosp Schleswig Holstein, Kiel, Germany; [141]Univ Kiel, Inst Clin Mol Biol, Kiel, Germany; [142]Univ La Laguna, Hosp Univ NS de Candelaria, Res Unit, Tenerife, Spain; [143]Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain; [144]Univ Chicago, Sect Pulm & Crit Care Med, Chicago, IL 60637 USA; [145]STAR, Genome Inst Singapore, Human Genet, Singapore, Singapore; [146]Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Lab Med & Genet, Seoul, South Korea; [147]INSERM, U1052, Canc Res Ctr Lyon, Lyon, France; [148]PSL Univ, Inst Curie, INSERM, U830, Paris, France; [149]Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA; [150]Univ Hong Kong, Li Ka Shing Fac Med, Dept Surg, Hong Kong, Hong Kong, Peoples R China; [151]Chang Gung Mem Hosp Lin Kou, Dept Otolaryngol Head & Neck Surg, Taoyuan, Taiwan; [152]Chang Gung Univ, Coll Med, Mol Med Res Ctr, Dept Biomed Sci Grad,Inst Biomed Sci, Taoyuan, Taiwan; [153]Chang Gung Univ, Mol Med Res Ctr, Taoyuan, Taiwan; [154]Flinders Univ S Australia, Sch Psychol, Adelaide, SA, Australia; [155]Soongsil Univ, Sch Syst Biomed Sci, Seoul, South Korea; [156]RIKEN, Ctr Integrat Med Sci, Tsurumi Ku, Suehiro Cho, Yokohama, Kanagawa, Japan; [157]Kobe Univ, Grad Sch Med, Div Mol Brain Sci, Chuo Ku, Kobe, Hyogo, Japan; [158]Univ Chicago, Ctr Personalized Therapeut, Chicago, IL 60637 USA; [159]NHLBIs Framingham Heart Study, Framingham, MA USA; [160]NHLBI, Populat Sci Branch, Bldg 10, Bethesda, MD 20892 USA; [161]Weill Cornell Med Qatar, Dept Med Genet, Doha, Qatar; [162]Wellcome Trust Sanger Inst, Human Genet, Genome Campus, Cambridge, England; [163]Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA; [164]Columbia Univ, Med Ctr, Dept Med, New York, NY USA; [165]Columbia Univ, Med Ctr, Dept Epidemiol, New York, NY USA; [166]Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA; [167]Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA; [168]Singapore Eye Res Inst, Singapore, Singapore; [169]Natl Eye Ctr, Singapore, Singapore; [170]Natl Univ Singapore, Dept Ophthalmol, Singapore, Singapore; [171]Natl Univ Hlth Syst, Singapore, Singapore; [172]Duke NUS Med Sch, Singapore, Singapore; [173]Capital Med Univ, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Inst Ophthalmol, Beijing Tongren Eye Ctr,Beijing Tongren Hosp, Beijing, Peoples R China; [174]Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany; [175]Kings Coll London, Inst Psychiat Psychol & Neurosci, Maurice Wohl Clin Neurosci Inst, Dept Basic & Clin Neurosci, London, England; [176]Univ Washington, Dept Biostat, Seattle, WA 98195 USA; [177]Univ Bristol, Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res Bristol Nutr Biomed Res Unit, Bristol, England
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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.

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出版当年[2017]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
最新[2023]版:
大类 | 1 区 医学
小类 | 1 区 肿瘤学
第一作者:
第一作者机构: [1]Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England; [2]Univ Bristol, Sch Social & Community Med, Bristol, Avon, England;
通讯作者:
通讯机构: [1]Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England; [2]Univ Bristol, Sch Social & Community Med, Bristol, Avon, England;
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