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Int J Cancer. 2015 Nov 1;137(9):2175-83. doi: 10.1002/ijc.29590. Epub 2015 Jun 19.

TERT gene harbors multiple variants associated with pancreatic cancer susceptibility.

Author information

  • 1Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 2Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 3Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • 4Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy.
  • 5Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic.
  • 6Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada.
  • 7Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy.
  • 8Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
  • 9Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
  • 10Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
  • 11Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  • 12Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany.
  • 13Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
  • 14Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 15Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
  • 16Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN.
  • 17Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy.
  • 18Surgical and Oncological Department, Pancreas Institute - University and Hospital Trust of Verona, Verona, Italy.
  • 19Department of Surgery, Second Faculty of Medicine, Charles University in Prague and Central Military Hospital, Prague, Czech Republic.
  • 201st Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece.
  • 21Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
  • 22Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX.
  • 23National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom.
  • 24Department of Surgery, Gastroenterology and Oncology (DISCOG), University of Padua, Padua, Italy.
  • 25Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
  • 26Department of Oncology, Palacky University Medical School and Teaching Hospital in Olomouc, Olomouc, Czech Republic.
  • 27Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy.
  • 28German Cancer Consortium (DKTK), Heidelberg, Germany.
  • 29MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
  • 30Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
  • 31Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
  • 32Department of Medicine - DIMED, University of Padua, Padua, Italy.
  • 33Department of Epidemiology and Public Health, Yale School of Public Health, New Haven, CT.
  • 34Department of Epidemiology, Harvard School of Public Health, Boston, MA.
  • 35Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA.
  • 36Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
  • 37Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
  • 38Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland.
  • 39Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
  • 40Division of Epidemiology, Departments of Obstetrics and Gynecology, Environmental Medicine, and Population Health, New York University School of Medicine, New York, NY.
  • 41Surgical Clinic 4, University of Padua, Padua, Italy.
  • 42Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic.
  • 43Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo Della Sofferenza,", San Giovanni Rotondo, Italy.
  • 44Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
  • 45ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
  • 46Epidemiology Research Program, American Cancer Society, Atlanta, GA.
  • 47Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
  • 48Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
  • 49Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy.
  • 50Department of Biology, University of Pisa, Pisa, Italy.
  • 51Department of Epidemiology, University of Washington, Seattle, WA.
  • 52Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.

Abstract

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.

© 2015 UICC.

KEYWORDS:

pancreatic cancer; polymorphisms; susceptibility; telomerase

PMID:
25940397
[PubMed - indexed for MEDLINE]
PMCID:
PMC4548797
[Available on 2016-11-01]

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