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TERT gene harbors multiple variants associated with pancreatic cancer susceptibility
D. Campa, C. Rizzato, R. Stolzenberg-Solomon, P. Pacetti, P. Vodicka, SP. Cleary, G. Capurso, HB. Bueno-de-Mesquita, J. Werner, M. Gazouli, K. Butterbach, A. Ivanauskas, N. Giese, GM. Petersen, P. Fogar, Z. Wang, C. Bassi, M. Ryska, GE....
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
PubMed
25940397
DOI
10.1002/ijc.29590
Knihovny.cz E-resources
- MeSH
- Adult MeSH
- Carcinoma, Pancreatic Ductal genetics MeSH
- Genetic Predisposition to Disease MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Mutation MeSH
- Pancreatic Neoplasms genetics MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Telomerase genetics MeSH
- Linkage Disequilibrium MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.
1st Department of Propaedeutic Surgery School of Medicine University of Athens Athens Greece
ARC NET Centre for Applied Research on Cancer University and Hospital Trust of Verona Verona Italy
Blood Transfusion Service Azienda Ospedaliero Universitaria Meyer Florence Italy
Department of Biology University of Pisa Pisa Italy
Department of Digestive Tract Diseases Medical University of Łodz Łodz Poland
Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY
Department of Epidemiology and Biostatistics University of California San Francisco San Francisco CA
Department of Epidemiology and Public Health Yale School of Public Health New Haven CT
Department of Epidemiology Harvard School of Public Health Boston MA
Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD
Department of Epidemiology University of Washington Seattle WA
Department of Gastroenterology Lithuanian University of Health Sciences Kaunas Lithuania
Department of General Surgery University Hospital Heidelberg Heidelberg Germany
Department of Health Sciences Research Mayo Clinic College of Medicine Rochester MN
Department of Hematology Institute of Hematology and Transfusion Medicine Warsaw Poland
Department of Laboratory Medicine University Hospital of Padua Padua Italy
Department of Medical Oncology Dana Farber Cancer Institute Boston MA
Department of Medicine DIMED University of Padua Padua Italy
Department of Oncology The Johns Hopkins University School of Medicine Baltimore MD
Department of Surgery Gastroenterology and Oncology University of Padua Padua Italy
Department of Surgery Unit of Experimental Surgical Pathology University Hospital of Pisa Pisa Italy
Department of Surgery University Health Network University of Toronto Toronto ON Canada
Department of Toxicogenomics National Institute of Public Health Prague Czech Republic
Digestive and Liver Disease Unit S Andrea Hospital 'Sapienza' University of Rome Rome Italy
Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany
Division of Public Health Sciences Fred Hutchinson Cancer Research Center Seattle WA
Epidemiology Research Program American Cancer Society Atlanta GA
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
References provided by Crossref.org
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- $a Campa, Daniele $u Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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- $a TERT gene harbors multiple variants associated with pancreatic cancer susceptibility / $c D. Campa, C. Rizzato, R. Stolzenberg-Solomon, P. Pacetti, P. Vodicka, SP. Cleary, G. Capurso, HB. Bueno-de-Mesquita, J. Werner, M. Gazouli, K. Butterbach, A. Ivanauskas, N. Giese, GM. Petersen, P. Fogar, Z. Wang, C. Bassi, M. Ryska, GE. Theodoropoulos, C. Kooperberg, D. Li, W. Greenhalf, C. Pasquali, T. Hackert, CS. Fuchs, B. Mohelnikova-Duchonova, C. Sperti, N. Funel, AK. Dieffenbach, NJ. Wareham, J. Buring, I. Holcátová, E. Costello, CF. Zambon, J. Kupcinskas, HA. Risch, P. Kraft, PM. Bracci, R. Pezzilli, SH. Olson, HD. Sesso, P. Hartge, O. Strobel, E. Małecka-Panas, K. Visvanathan, AA. Arslan, S. Pedrazzoli, P. Souček, D. Gioffreda, TJ. Key, R. Talar-Wojnarowska, A. Scarpa, A. Mambrini, EJ. Jacobs, K. Jamroziak, A. Klein, F. Tavano, F. Bambi, S. Landi, MA. Austin, L. Vodickova, H. Brenner, SJ. Chanock, G. Delle Fave, A. Piepoli, M. Cantore, W. Zheng, BM. Wolpin, LT. Amundadottir, F. Canzian,
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- $a A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.
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