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Article Dans Une Revue European Urology Année : 2017

Genetic variants related to longer telomere length are associated with increased risk of renal cell carcinoma

Mitchell Machiela (1) , Jonathan Hofmann (1) , Robert Carreras-Torres (2) , Kevin Brown (1) , Mattias Johansson (2) , Zhaoming Wang (3) , Matthieu Foll (2) , Peng Li (2) , Nathaniel Rothman (1) , Sharon Savage (1) , Valerie Gaborieau (2) , James Mckay (2) , Yuanqing Ye (4) , Marc Henrion (5) , Fiona Bruinsma (6) , Susan Jordan (7, 8) , Gianluca Severi (6, 9, 10) , Kristian Hveem (11) , Lars J. Vatten (11) , Tony Fletcher (12) , Kvetoslava Koppova (13) , Susanna Larsson (14) , Alicja Wolk (14) , Rosamonde Banks (15) , Peter Selby (15) , Douglas Easton (16) , Paul Pharoah (16) , Gabriella Andreotti (17) , Laura Freeman (17) , Stella Koutros (17) , Demetrius Albanes (17) , Satu Mannisto (18) , Stephanie Weinstein (17) , Peter Clark (19) , Todd Edwards (19) , Loren Lipworth (19) , Susan Gapstur (20) , Victoria Stevens (20) , Hallie Carol (21) , Matthew Freedman (21) , Mark Pomerantz (21) , Eunyoung Cho (22) , Peter Kraft (23) , Mark Preston (24) , Kathryn Wilson (23) , J. Michael Gaziano (25, 24) , Howard Sesso (23) , Amanda Black (1) , Neal Freedman (1) , Wen-Yi Huang (1) , John Anema (26) , Richard Kahnoski (26) , Brian Lane (27) , Sabrina Noyes (28) , David Petillo (28) , Leandro Colli (17) , Joshua Sampson (17) , Celine Besse (29) , Helene Blanche (30) , Anne Boland (29) , Laurie Burdette (17) , Egor Prokhortchouk (31) , Konstantin Skryabin (31) , Meredith Yeager (17) , Mirjana Mijuskovic (32) , Miodrag Ognjanovic (32) , Lenka Foretova (32) , Ivana Holcatova (33) , Vladimir Janout (34) , Dana Mates (35) , Anush Mukeriya (36) , Stefan Rascu (37) , David Zaridze (36) , Vladimir Bencko (38) , Cezary Cybulski (34) , Eleonora Fabianova (39) , Viorel Jinga (38) , Jolanta Lissowska (40) , Jan Lubinski (41) , Marie Navratilova (33) , Peter Rudnai (42) , Neonila Szeszenia-Dabrowska (43) , Simone Benhamou (44, 45, 46) , Geraldine Cancel-Tassin (47, 48) , Olivier Cussenot (47, 48, 49) , H. Bas Bueno-De-Mesquita (50, 51, 52, 53) , Federico Canzian (54) , Eric Duell (55) , Börje Ljungberg (56) , Raviprakash Sitaram (56) , Ulrike Peters (57) , Emily White (57) , Garnet Anderson (57) , Lisa Johnson (57) , Juhua Luo (58) , Julie Buring (23) , I-Min Lee (23, 24) , Wong-Ho Chow (4) , Lee Moore (17) , Christopher Wood (4) , Timothy Eisen (16) , James Larkin (59) , Toni Choueiri (21) , G. Mark Lathrop (60) , Bin Tean Teh , Jean-Francois Deleuze (29, 30) , Xifeng Wu (28) , Richard Houlston (61) , Paul Brennan (2) , Stephen Chanock (1) , Ghislaine Scelo (2) , Mark Purdue (1)
1 NCI-NIH - National Cancer Institute [Bethesda]
2 CIRC - IARC - Centre International de Recherche contre le Cancer - International Agency for Research on Cancer
3 St Jude Children's Research Hospital
4 The University of Texas M.D. Anderson Cancer Center [Houston]
5 MSSM - Icahn School of Medicine at Mount Sinai [New York]
6 Cancer Council Victoria
7 QIMR Berghofer Medical Research Institute
8 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
9 Melbourne School of Population and Global Health [Melbourne]
10 CESP - Centre de recherche en épidémiologie et santé des populations
11 NTNU - Norwegian University of Science and Technology [Trondheim]
12 LSHTM - London School of Hygiene and Tropical Medicine
13 RAPH - Regional Authority of Public Health [Slovaquia]
14 Karolinska Institutet [Stockholm]
15 University of Leeds
16 CAM - University of Cambridge [UK]
17 NIH - National Institutes of Health [Bethesda, MD, USA]
18 National Institute for Health and Welfare [Helsinki]
19 VICC - Vanderbilt-Ingram Cancer Center
20 American Cancer Society [Atlanta, GA, USA]
21 Dana-Farber Cancer Institute [Boston]
22 Brown University
23 Harvard T.H. Chan School of Public Health
24 Brigham and Women’s Hospital [Boston, MA]
25 Veterans Administration
26 Spectrum Health [Grand Rapids]
27 MSUCUM - Michigan State University College of Human Medicine [Grand Rapids, MI, USA]
28 Van Andel Institute [Grand Rapids]
29 CNRGH - Centre National de Recherche en Génomique Humaine
30 CEPH - Centre d'Etude du Polymorphisme Humain
31 RAS - Russian Academy of Sciences [Moscow]
32 IOCPR - International Organization for Cancer Prevention and Research [Belgrade, Serbia]
33 MMCI - Masaryk Memorial Cancer Institute
34 Charles University, Faculty of Education [Prague]
35 Palacky University Olomouc
36 RHL - National Institute of Public Health, Radiation Hygiene Laboratory, Bucharest
37 N.N. Blokhin Russian Cancer Research Center
38 UMPCD - University of Medicine and Pharmacy “Carol Davila” Bucharest
39 Department of Epidemiology, Regional Authority of Public Health in Banská Bystrica
40 MCMCC - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
41 PUM - Pomeranian Medical University [Szczecin]
42 National Public Health Center, National Directorate of Environmental Health, 1097 Budapest
43 Institute of Occupational Medicine [ Lodz, Poland]
44 U946 - Variabilité Génétique et Maladies Humaines
45 IGR - Institut Gustave Roussy
46 CNRS UMR 8200 - Réparation de l’ADN
47 CeRePP - Centre de Recherche pour les Pathologies Prostatiques [Paris]
48 IUC - Institut Universitaire de Cancérologie [Sorbonne Université]
49 CHU Tenon [AP-HP]
50 RIVM - National Institute for Public Health and the Environment [Bilthoven]
51 UMCU - University Medical Center [Utrecht]
52 Imperial College London
53 UM - University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie]
54 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)
55 ICO - Catalan Institute of Oncology = Instituto Catalán de Oncología
56 Umeå University, Sweden
57 FHCRC - Fred Hutchinson Cancer Research Center [Seattle]
58 Indiana University [Bloomington]
59 The Royal Marsden NHS Foundation Trust [London]
60 McGill University = Université McGill [Montréal, Canada]
61 The institute of cancer research [London]
Peter Selby
  • Fonction : Auteur
Eunyoung Cho
  • Fonction : Auteur
Bin Tean Teh
  • Fonction : Auteur

Résumé

BackgroundRelative 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.ObjectiveWe performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.Design, setting, and participantsGenotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.Outcome measurements and statistical analysisOdds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.Results and limitationsLonger genetically inferred telomere length was associated with an increased risk of RCC (OR = 2.07 per predicted kilobase increase, 95% confidence interval [CI]: = 1.70–2.53, p < 0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2 > 0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR = 1.73, 95% CI = 1.36–2.21, p < 0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N = 5573, OR = 1.93, 95% CI = 1.50–2.49, p < 0.0001), papillary (N = 573, OR = 1.96, 95% CI = 1.01–3.81, p = 0.046), and chromophobe RCC (N = 203, OR = 2.37, 95% CI = 0.78–7.17, p = 0.13).ConclusionsOur investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.Patient summaryTelomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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cea-04475372 , version 1 (18-06-2024)

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Mitchell Machiela, Jonathan Hofmann, Robert Carreras-Torres, Kevin Brown, Mattias Johansson, et al.. Genetic variants related to longer telomere length are associated with increased risk of renal cell carcinoma. European Urology, 2017, 72 (5), pp.747-754. ⟨10.1016/j.eururo.2017.07.015⟩. ⟨cea-04475372⟩
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