Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study
Daniele Campa
Department of Biology, University of Pisa, Pisa, Italy
Search for more papers by this authorMartina Matarazzi
Department of Biology, University of Pisa, Pisa, Italy
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorWilliam Greenhalf
Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom
Search for more papers by this authorMaarten Bijlsma
Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
Search for more papers by this authorKai-Uwe Saum
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorClaudio Pasquali
Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
Search for more papers by this authorHanneke van Laarhoven
Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
Search for more papers by this authorAndrea Szentesi
Institute for Translational Medicine, University of Pécs, Pécs, Hungary
First Department of Medicine, University of Szeged, Szeged, Hungary
Search for more papers by this authorFrancesca Federici
Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy
Search for more papers by this authorPavel Vodicka
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic
Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
Search for more papers by this authorNiccola Funel
Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy
Search for more papers by this authorRaffaele Pezzilli
Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy
Search for more papers by this authorH. Bas Bueno-de-Mesquita
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Search for more papers by this authorLudmila Vodickova
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic
Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
Search for more papers by this authorDaniela Basso
Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy
Search for more papers by this authorOfure Obazee
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorThilo Hackert
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorPavel Soucek
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
Search for more papers by this authorKatarina Cuk
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorJörg Kaiser
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorCosimo Sperti
Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
Search for more papers by this authorMartin Lovecek
Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
Search for more papers by this authorGabriele Capurso
Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University, Rome, Italy
PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Search for more papers by this authorBeatrice Mohelnikova-Duchonova
Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
Search for more papers by this authorKay-Tee Khaw
University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom
Search for more papers by this authorAnna-Katharina König
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorJuozas Kupcinskas
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Search for more papers by this authorRudolf Kaaks
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorFranco Bambi
Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy
Search for more papers by this authorLivia Archibugi
Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University, Rome, Italy
PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Search for more papers by this authorAndrea Mambrini
Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy
Search for more papers by this authorGiulia Martina Cavestro
Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorStefano Landi
Department of Biology, University of Pisa, Pisa, Italy
Search for more papers by this authorPéter Hegyi
Institute for Translational Medicine, University of Pécs, Pécs, Hungary
First Department of Medicine, University of Szeged, Szeged, Hungary
MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary
Search for more papers by this authorJakob R. Izbicki
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorDomenica Gioffreda
Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorCarlo Federico Zambon
Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
Search for more papers by this authorFrancesca Tavano
Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorRenata Talar-Wojnarowska
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
Search for more papers by this authorKrzysztof Jamroziak
Institute of Hematology and Transfusion Medicine, Warsaw, Poland
Search for more papers by this authorTimothy J. Key
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorGianfranco Delle Fave
Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University, Rome, Italy
Search for more papers by this authorOliver Strobel
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorLaimas Jonaitis
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Search for more papers by this authorAngelo Andriulli
Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorRita T. Lawlor
ARC-NET, University and Hospital Trust of Verona, Verona, Italy
Search for more papers by this authorFelice Pirozzi
Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorVerena Katzke
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorChiara Valsuani
Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy
Search for more papers by this authorYogesh K. Vashist
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorHermann Brenner
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Federico Canzian
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
Correspondence to: Federico Canzian, Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, E-mail: [email protected]; Tel. +49–6221-421791; Fax +49–6221-421810Search for more papers by this authorDaniele Campa
Department of Biology, University of Pisa, Pisa, Italy
Search for more papers by this authorMartina Matarazzi
Department of Biology, University of Pisa, Pisa, Italy
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorWilliam Greenhalf
Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom
Search for more papers by this authorMaarten Bijlsma
Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
Search for more papers by this authorKai-Uwe Saum
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorClaudio Pasquali
Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
Search for more papers by this authorHanneke van Laarhoven
Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands
Search for more papers by this authorAndrea Szentesi
Institute for Translational Medicine, University of Pécs, Pécs, Hungary
First Department of Medicine, University of Szeged, Szeged, Hungary
Search for more papers by this authorFrancesca Federici
Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy
Search for more papers by this authorPavel Vodicka
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic
Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
Search for more papers by this authorNiccola Funel
Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy
Search for more papers by this authorRaffaele Pezzilli
Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy
Search for more papers by this authorH. Bas Bueno-de-Mesquita
Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
Search for more papers by this authorLudmila Vodickova
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic
Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
Search for more papers by this authorDaniela Basso
Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy
Search for more papers by this authorOfure Obazee
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorThilo Hackert
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorPavel Soucek
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
Search for more papers by this authorKatarina Cuk
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorJörg Kaiser
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorCosimo Sperti
Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
Search for more papers by this authorMartin Lovecek
Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic
Search for more papers by this authorGabriele Capurso
Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University, Rome, Italy
PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Search for more papers by this authorBeatrice Mohelnikova-Duchonova
Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
Search for more papers by this authorKay-Tee Khaw
University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom
Search for more papers by this authorAnna-Katharina König
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorJuozas Kupcinskas
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Search for more papers by this authorRudolf Kaaks
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorFranco Bambi
Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy
Search for more papers by this authorLivia Archibugi
Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University, Rome, Italy
PancreatoBiliary Endoscopy and EUS Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Search for more papers by this authorAndrea Mambrini
Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy
Search for more papers by this authorGiulia Martina Cavestro
Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy
Search for more papers by this authorStefano Landi
Department of Biology, University of Pisa, Pisa, Italy
Search for more papers by this authorPéter Hegyi
Institute for Translational Medicine, University of Pécs, Pécs, Hungary
First Department of Medicine, University of Szeged, Szeged, Hungary
MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary
Search for more papers by this authorJakob R. Izbicki
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorDomenica Gioffreda
Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorCarlo Federico Zambon
Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy
Search for more papers by this authorFrancesca Tavano
Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorRenata Talar-Wojnarowska
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland
Search for more papers by this authorKrzysztof Jamroziak
Institute of Hematology and Transfusion Medicine, Warsaw, Poland
Search for more papers by this authorTimothy J. Key
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorGianfranco Delle Fave
Digestive and Liver Disease Unit, S. Andrea Hospital, ‘Sapienza’ University, Rome, Italy
Search for more papers by this authorOliver Strobel
Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
Search for more papers by this authorLaimas Jonaitis
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Search for more papers by this authorAngelo Andriulli
Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorRita T. Lawlor
ARC-NET, University and Hospital Trust of Verona, Verona, Italy
Search for more papers by this authorFelice Pirozzi
Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy
Search for more papers by this authorVerena Katzke
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorChiara Valsuani
Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy
Search for more papers by this authorYogesh K. Vashist
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Search for more papers by this authorHermann Brenner
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Federico Canzian
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
Correspondence to: Federico Canzian, Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany, E-mail: [email protected]; Tel. +49–6221-421791; Fax +49–6221-421810Search for more papers by this authorAbstract
Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score (“teloscore”, which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35–1.76; p = 1.54 × 10−10) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73–0.88; p = 1.87 × 10−6, ptrend = 3.27 × 10−7). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10−9 for highest vs. lowest quintile; p = 1.82 × 10−10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer.
Abstract
What's new?
How does lymphocyte telomere length affect pancreatic cancer risk? These authors analyzed 10 SNPs associated with telomere length and their relationship with pancreatic cancer risk, using data from the Pancreatic Disease Research (PANDoRA) consortium. Each patient received a “teloscore” based on the combined SNP data, and it turned out that a low teloscore - predicting a short telomere - was associated with increased pancreatic cancer risk. The researchers also identified for the first time a significant genome-wide association between a SNP, TERT-rs2736100, and increased pancreatic cancer risk. They also discovered a completely novel association between a SNP, NAF1-rs7675998, and decreased risk.
Supporting Information
| Filename | Description |
|---|---|
| ijc31928-sup-0001-supinfo.pdfWord 2007 document , 96.5 KB |
Supplementary Table 1. Examples of teloscore computation. Supplementary Table 2. Data on known risk factors for pancreatic cancer. Supplementary Table 3. Literature review on telomere length and PDAC risk. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1Hidalgo M, Cascinu S, Kleeff J, et al. Addressing the challenges of pancreatic cancer: future directions for improving outcomes. Pancreatology 2015; 15: 8–18.
- 2Barone E, Corrado A, Gemignani F, et al. Environmental risk factors for pancreatic cancer: an update. Arch Toxicol 2016; 90: 2617–42.
- 3Maisonneuve P, Lowenfels AB. Risk factors for pancreatic cancer: a summary review of meta-analytical studies. Int J Epidemiol 2015; 44: 186–98.
- 4Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 2009; 41: 986–90.
- 5Bao Y, Prescott J, Yuan C, et al. Leucocyte telomere length, genetic variants at the TERT gene region and risk of pancreatic cancer. Gut 2016; 66: 1116–22.
- 6Campa D, Pastore M, Gentiluomo M, et al. Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk. Oncotarget 2016; 7: 57011–20.
- 7Campa D, Rizzato C, Stolzenberg-Solomon R, et al. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. Int J Cancer 2015; 137: 2175–83.
- 8Childs EJ, Mocci E, Campa D, et al. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. Nat Genet 2015; 47: 911–6.
- 9Low SK, Kuchiba A, Zembutsu H, et al. Genome-wide association study of pancreatic cancer in Japanese population. PloS One 2010; 5: e11824.
- 10Petersen GM, Amundadottir L, Fuchs CS, et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 2010; 42: 224–8.
- 11Rizzato C, Campa D, Giese N, et al. Pancreatic cancer susceptibility loci and their role in survival. PloS One 2011; 6: e27921.
- 12Rizzato C, Campa D, Pezzilli R, et al. ABO blood groups and pancreatic cancer risk and survival: results from the PANcreatic disease ReseArch (PANDoRA) consortium. Oncol Rep 2013; 29: 1637–44.
- 13Rizzato C, Campa D, Talar-Wojnarowska R, et al. Association of genetic polymorphisms with survival of pancreatic ductal adenocarcinoma patients. Carcinogenesis 2016; 37: 957–64.
- 14Willis JA, Olson SH, Orlow I, et al. A replication study and genome-wide scan of single-nucleotide polymorphisms associated with pancreatic cancer risk and overall survival. Clin Cancer Res 2012; 18: 3942–51.
- 15Wolpin BM, Rizzato C, Kraft P, et al. Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 2014; 46: 994–1000.
- 16Wu C, Kraft P, Stolzenberg-Solomon R, et al. Genome-wide association study of survival in patients with pancreatic adenocarcinoma. Gut 2012; 63: 152–60.
- 17Wu C, Miao X, Huang L, et al. Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations. Nat Genet 2011; 44: 62–6.
- 18Zhang M, Wang Z, Obazee O, et al. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21. Oncotarget 2016; 7: 66328–43.
- 19Mocellin S, Verdi D, Pooley KA, et al. Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis. J Natl Cancer Inst 2012; 104: 840–54.
- 20Blackburn EH. Switching and signaling at the telomere. Cell 2001; 106: 661–73.
- 21Armanios M. Telomeres and age-related disease: how telomere biology informs clinical paradigms. J Clin Invest 2013; 123: 996–1002.
- 22Martinez P, Blasco MA. Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer 2011; 11: 161–76.
- 23McEachern MJ, Krauskopf A, Blackburn EH. Telomeres and their control. Annu Rev Genet 2000; 34: 331–58.
- 24Kimura M, Gazitt Y, Cao X, et al. Synchrony of telomere length among hematopoietic cells. Exp Hematol 2010; 38: 854–9.
- 25Wilson WR, Herbert KE, Mistry Y, et al. Blood leucocyte telomere DNA content predicts vascular telomere DNA content in humans with and without vascular disease. Eur Heart J 2008; 29: 2689–94.
- 26Lynch SM, Major JM, Cawthon R, et al. A prospective analysis of telomere length and pancreatic cancer in the alpha-tocopherol beta-carotene cancer (ATBC) prevention study. Int J Cancer 2013; 133: 2672–80.
- 27Skinner HG, Gangnon RE, Litzelman K, et al. Telomere length and pancreatic cancer: a case-control study. Cancer Epidemiol Biomarkers Prev 2012; 21: 2095–100.
- 28Campa D, Mergarten B, De Vivo I, et al. Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study. Cancer Epidemiol Biomarkers Prev 2014; 23: 2447–54.
- 29Zhang R, Zhao J, Xu J, et al. Association of peripheral leukocyte telomere length and its variation with pancreatic cancer and colorectal cancer risk in Chinese population. Oncotarget 2016; 7: 38579–85.
- 30Cunningham JM, Johnson RA, Litzelman K, et al. Telomere length varies by DNA extraction method: implications for epidemiologic research. Cancer Epidemiol Biomarkers Prev 2013; 22: 2047–54.
- 31Hou L, Zhang X, Gawron AJ, et al. Surrogate tissue telomere length and cancer risk: shorter or longer? Cancer Lett 2012; 319: 130–5.
- 32Pooley KA, Sandhu MS, Tyrer J, et al. Telomere length in prospective and retrospective cancer case-control studies. Cancer Res 2010; 70: 3170–6.
- 33Iles MM, Bishop DT, Taylor JC, et al. The effect on melanoma risk of genes previously associated with telomere length. J Natl Cancer Inst 2014; 106: dju267.
- 34Luu HN, Long J, Wen W, et al. Association between genetic risk score for telomere length and risk of breast cancer. Cancer Causes Control 2016; 27: 1219–28.
- 35Machiela MJ, Lan Q, Slager SL, et al. Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes. Hum Mol Genet 2016; 25: 1663–76.
- 36Walsh KM, Codd V, Rice T, et al. Longer genotypically-estimated leukocyte telomere length is associated with increased adult glioma risk. Oncotarget 2015; 6: 42468–77.
- 37Walsh KM, Codd V, Smirnov IV, et al. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nat Genet 2014; 46: 731–5.
- 38Zhang C, Doherty JA, Burgess S, et al. Genetic determinants of telomere length and risk of common cancers: a Mendelian randomization study. Hum Mol Genet 2015; 24: 5356–66.
- 39Antwi SO, Bamlet WR, Broderick BT, et al. Genetically predicted telomere length is not associated with pancreatic cancer risk. Cancer Epidemiol Biomarkers Prev 2017; 26: 971–4.
- 40Haycock PC, Burgess S, Nounu A, et al. Association between telomere length and risk of cancer and non-neoplastic diseases: a Mendelian randomization study. JAMA Oncol 2017; 3: 636–51.
- 41Campa D, Rizzato C, Capurso G, et al. Genetic susceptibility to pancreatic cancer and its functional characterisation: the PANcreatic disease ReseArch (PANDoRA) consortium. Dig Liver Dis 2013; 45: 95–9.
- 42Campa D, Martino A, Varkonyi J, et al. Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length. Int J Cancer 2015; 136: E351–8.
- 43Boyle AP, Hong EL, Hariharan M, et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res 2012; 22: 1790–7.
- 44Ward LD, Kellis M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 2012; 40: D930–4.
- 45 GTEX Consortium. The genotype-tissue expression (GTEx) project. Nat Genet 2013; 45: 580–5.
- 46Egan ED, Collins K. An enhanced H/ACA RNP assembly mechanism for human telomerase RNA. Mol Cell Biol 2012; 32: 2428–39.
- 47Klug A. The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu Rev Biochem 2010; 79: 213–31.
- 48Gu Y, Yu C, Miao L, et al. Telomere length, genetic variants and risk of squamous cell carcinoma of the head and neck in southeast Chinese. Sci Rep 2016; 6: 20675.
- 49van Heek NT, Meeker AK, Kern SE, et al. Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. Am J Pathol 2002; 161: 1541–7.
- 50Daniali L, Benetos A, Susser E, et al. Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun 2013; 4: 1597.
- 51Hunt SC, Chen W, Gardner JP, et al. Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute family heart study and the Bogalusa heart study. Aging Cell 2008; 7: 451–8.
- 52Codd V, Nelson CP, Albrecht E, et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat Genet 2013; 45: 427e1–2.
Citing Literature
