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Pancreatic Neoplasms: HELP
Articles by Hermann Brenner
Based on 18 articles published since 2009
(Why 18 articles?)
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Between 2009 and 2019, H. Brenner wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review A systematic review of serum autoantibodies as biomarkers for pancreatic cancer detection. 2016

Dumstrei, Karin / Chen, Hongda / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. · European Molecular Biology Organization (EMBO), D-69117 Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), D-69120 Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany. ·Oncotarget · Pubmed #26840568.

ABSTRACT: Pancreatic cancer is a leading cause of cancer-related deaths in the western world. Patients with pancreatic cancer have poor prognosis, partly due to difficulties in detecting it at early stages. While different markers have been associated with pancreatic cancer, many of them show suboptimal sensitivity and specificity. Serum autoantibodies against tumor-associated antigens have recently emerged as early stage biomarkers for different types of cancers. Given the urgent need for early and reliable biomarkers for pancreatic cancer, we undertook a systematic review of the published literature to identify primary articles that evaluated serum autoantibodies in pancreatic cancer detection by searching PubMed and ISI Web of Knowledge. Two reviewers extracted data on study characteristics and results independently. Overall, 31 studies evaluating 124 individual serum autoantibodies in pancreatic cancer detection met the inclusion criteria. In general, single autoantibody markers showed relatively low sensitivities at high specificity. A combination of markers, either multiple serum autoantibodies or serum autoantibodies combined with tumor-associated markers, led to a better diagnostic performance. However, most of the analyzed autoantibodies have only been reported in single studies and therefore need to be independently validated. We conclude that serum autoantibodies might present an option as biomarkers for early detection of pancreatic cancer, but more work is needed to identify and validate autoantibody signatures that are associated with early stage pancreatic cancer.

2 Article Development and validation of a prognostic model to predict the prognosis of patients who underwent chemotherapy and resection of pancreatic adenocarcinoma: a large international population-based cohort study. 2019

Huang, Lei / Balavarca, Yesilda / van der Geest, Lydia / Lemmens, Valery / Van Eycken, Liesbet / De Schutter, Harlinde / Johannesen, Tom B / Zadnik, Vesna / Primic-Žakelj, Maja / Mägi, Margit / Grützmann, Robert / Besselink, Marc G / Schrotz-King, Petra / Brenner, Hermann / Jansen, Lina. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. · Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · Netherlands Cancer Registry (NCR), Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands. · Belgian Cancer Registry (BCR), Brussels, Belgium. · Registry Department, The Cancer Registry of Norway (CRN), Oslo, Norway. · Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Ljubljana, Slovenia. · Estonian Cancer Registry, National Institute for Health Development, Tallinn, Estonia. · Department of Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany. · Dutch Pancreatic Cancer Group (DPCG), Department of Surgery, Cancer Center Amsterdam, Amsterdam University Medical Centers (UMC), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. l.jansen@dkfz-heidelberg.de. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. l.jansen@dkfz-heidelberg.de. ·BMC Med · Pubmed #30905320.

ABSTRACT: BACKGROUND: Pancreatic cancer (PaC) remains extremely lethal worldwide even after resection. PaC resection rates are low, making prognostic studies in resected PaC difficult. This large international population-based study aimed at exploring factors associated with survival in patients with resected TNM stage I-II PaC receiving chemotherapy and at developing and internationally validating a survival-predicting model. METHODS: Data of stage I-II PaC patients resected and receiving chemotherapy in 2003-2014 were obtained from the national cancer registries of Belgium, the Netherlands, Slovenia, and Norway, and the US Surveillance, Epidemiology, and End Results (SEER)-18 Program. Multivariable Cox proportional hazards models were constructed to investigate the associations of patient and tumor characteristics with overall survival, and analysis was performed in each country respectively without pooling. Prognostic factors remaining after backward selection in SEER-18 were used to build a nomogram, which was subjected to bootstrap internal validation and external validation using the European datasets. RESULTS: A total of 11,837 resected PaC patients were analyzed, with median survival time of 18-23 months and 3-year survival rates of 21-31%. In the main analysis, patient age, tumor T stage, N stage, and differentiation were associated with survival across most countries, with country-specific association patterns and strengths. However, tumor location was mostly not significantly associated with survival. Resection margin, hospital type, tumor size, positive and harvested lymph node number, lymph node ratio, and comorbidity number were associated with survival in certain countries where the information was available. A median survival time- and 1-, 2-, 3-, and 5-year survival probability-predictive nomogram incorporating the backward-selected variables in the main analysis was established. It fits each European national cohort similarly well. Calibration curves showed very good agreement between nomogram-prediction and actual observation. The concordance index of the nomogram (0.60) was significantly higher than that of the T and N stage-based model (0.56) for predicting survival. CONCLUSIONS: In these large international population-based cohorts, patients with resected PaC receiving chemotherapy have distinct characteristics independently associated with survival, with country-specific patterns and strengths. A robust benchmark population-based survival-predicting model is established and internationally validated. Like previous models predicting survival in resected PaC, our nomogram performs modestly.

3 Article Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study. 2019

Campa, Daniele / Matarazzi, Martina / Greenhalf, William / Bijlsma, Maarten / Saum, Kai-Uwe / Pasquali, Claudio / van Laarhoven, Hanneke / Szentesi, Andrea / Federici, Francesca / Vodicka, Pavel / Funel, Niccola / Pezzilli, Raffaele / Bueno-de-Mesquita, H Bas / Vodickova, Ludmila / Basso, Daniela / Obazee, Ofure / Hackert, Thilo / Soucek, Pavel / Cuk, Katarina / Kaiser, Jörg / Sperti, Cosimo / Lovecek, Martin / Capurso, Gabriele / Mohelnikova-Duchonova, Beatrice / Khaw, Kay-Tee / König, Anna-Katharina / Kupcinskas, Juozas / Kaaks, Rudolf / Bambi, Franco / Archibugi, Livia / Mambrini, Andrea / Cavestro, Giulia Martina / Landi, Stefano / Hegyi, Péter / Izbicki, Jakob R / Gioffreda, Domenica / Zambon, Carlo Federico / Tavano, Francesca / Talar-Wojnarowska, Renata / Jamroziak, Krzysztof / Key, Timothy J / Fave, Gianfranco Delle / Strobel, Oliver / Jonaitis, Laimas / Andriulli, Angelo / Lawlor, Rita T / Pirozzi, Felice / Katzke, Verena / Valsuani, Chiara / Vashist, Yogesh K / Brenner, Hermann / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Pancreatic and Digestive Endocrine Surgery - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · First Department of Medicine, University of Szeged, Szeged, Hungary. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Italy. · 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. · Department of Surgery, Unit of Experimental Surgical Pathology, University of Pisa, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · 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. · Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Third Surgical Clinic - Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · 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. · Department of Oncology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. · University of Cambridge School of Clinical Medicine Clinical Gerontology Unit, Addenbrooke's Hospital, Cambridge, United Kingdom. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · MTA-SZTE Momentum Translational Gastroenterology Research Group, Szeged, Hungary. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Molecular Biology Lab, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET, University and Hospital Trust of Verona, Verona, Italy. · Division of Abdominal Surgery, IRCCS Ospedale Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. · 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. ·Int J Cancer · Pubmed #30325019.

ABSTRACT: 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

4 Article Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations. 2019

Huang, Lei / Jansen, Lina / Balavarca, Yesilda / Molina-Montes, Esther / Babaei, Masoud / van der Geest, Lydia / Lemmens, Valery / Van Eycken, Liesbet / De Schutter, Harlinde / Johannesen, Tom B / Fristrup, Claus W / Mortensen, Michael B / Primic-Žakelj, Maja / Zadnik, Vesna / Becker, Nikolaus / Hackert, Thilo / Mägi, Margit / Cassetti, Tiziana / Sassatelli, Romano / Grützmann, Robert / Merkel, Susanne / Gonçalves, Ana F / Bento, Maria J / Hegyi, Péter / Lakatos, Gábor / Szentesi, Andrea / Moreau, Michel / van de Velde, Tony / Broeks, Annegien / Sant, Milena / Minicozzi, Pamela / Mazzaferro, Vincenzo / Real, Francisco X / Carrato, Alfredo / Molero, Xavier / Besselink, Marc G / Malats, Núria / Büchler, Markus W / Schrotz-King, Petra / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · German Cancer Consortium (DKTK), 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. · Geneticand Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, ISCIII, Madrid, Spain. · Netherlands Cancer Registry (NCR), Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, Netherlands. · Belgian Cancer Registry (BCR), Brussels, Belgium. · Registry Department, The Cancer Registry of Norway (CRN), Oslo, Norway. · Danish Pancreatic Cancer Database (DPCD), Odense, Denmark. · Danish Pancreatic Cancer Group, HPB Section, Department of Surgery, Odense University Hospital, Odense, Denmark. · Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Ljubljana, Slovenia. · Clinical Cancer Registry, DKFZ and NCT, Heidelberg, Germany. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Estonian Cancer Registry, National Institute for Health Development, Tallinn, Estonia. · Pancreatic Cancer Registry of Reggio Emilia Province, Unit of Gastroenterology and Digestive Endoscopy AUSL-RE, Local Health Authority-IRCCS, Reggio Emilia, Italy. · Department of Surgery, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany. · Departments of Epidemiology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal. · Institute for Translational Medicine, University of Pécs, Pécs, Hungary. · Department of Oncology, St. Istvan and St. Laszlo Hospital and Out-Patient Department, Budapest, Hungary. · Department of Surgical Oncology, Jules Bordet Institute (IJB), Brussels, Belgium. · Biometrics Department, The Netherlands Cancer Institute (NKI), Amsterdam, Netherlands. · Analytical Epidemiology and Health Impact Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy. · Hepato-Biliary Surgery Unit, Istituto Nazionale dei Tumori (INT), and University of Milan, Milan, Italy. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), CIBERONC, Madrid, Spain. · Department de Ciencies Experimentals i de la, Universitat Pompeu Fabra, Barcelona, Spain. · Department of Oncology, Ramon y Cajal University Hospital, IRYCIS, Alcala University, CIBERONC, Madrid, Spain. · Hospital Universitari Vall d'Hebron, Exocrine Pancreas Research Unit and Vall d'Hebron Research Institute (VHIR), Universitat Autonoma de Barcelona, Campus de la UAB, Barcelona, Spain. · CIBEREHD and CIBERESP, Madrid, Spain. · Dutch Pancreatic Cancer Group, Academic Medical Centre Amsterdam, Amsterdam, Netherlands. ·Gut · Pubmed #29158237.

ABSTRACT: OBJECTIVE: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation. DESIGN: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed. Age-standardised resection rates for overall and stage I-II PaCs were computed. Associations between resection and demographic and clinical parameters were assessed using multivariable logistic regression models. RESULTS: A total of 153 698 records were analysed. In population-based registries in 2012-2014, resection rates ranged from 13.2% (Estonia) to 21.2% (Slovenia) overall and from 34.8% (Norway) to 68.7% (Denmark) for stage I-II tumours, with great international variations. During 2003-2014, resection rates only increased in USA, the Netherlands and Denmark. Resection was significantly less frequently performed with more advanced tumour stage (ORs for stage III and IV versus stage I-II tumours: 0.05-0.18 and 0.01-0.06 across countries) and increasing age (ORs for patients 70-79 and ≥80 versus those <60 years: 0.37-0.63 and 0.03-0.16 across countries). Patients with advanced-stage tumours (stage III-IV: 63.8%-81.2%) and at older ages (≥70 years: 52.6%-59.5%) receiving less frequently resection comprised the majority of diagnosed cases. Patient performance status, tumour location and size were also associated with resection application. CONCLUSION: Rates of PaC resection remain low in Europe and USA with great international variations. Further studies are warranted to explore reasons for these variations.

5 Article Stratified survival of resected and overall pancreatic cancer patients in Europe and the USA in the early twenty-first century: a large, international population-based study. 2018

Huang, Lei / Jansen, Lina / Balavarca, Yesilda / Babaei, Masoud / van der Geest, Lydia / Lemmens, Valery / Van Eycken, Liesbet / De Schutter, Harlinde / Johannesen, Tom B / Primic-Žakelj, Maja / Zadnik, Vesna / Besselink, Marc G / Schrotz-King, Petra / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. · Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Preventive Oncology, DKFZ and National Center for Tumor Diseases (NCT), Heidelberg, Germany. · The Netherlands Cancer Registry, The Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands. · Belgian Cancer Registry (BCR), Brussels, Belgium. · Cancer Registry of Norway (CRN), Oslo, Norway. · Cancer Registry of Slovenia (CRS), Ljubljana, Slovenia. · Dutch Pancreatic Cancer Group, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. h.brenner@dkfz-heidelberg.de. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz-heidelberg.de. · Division of Preventive Oncology, DKFZ and National Center for Tumor Diseases (NCT), Heidelberg, Germany. h.brenner@dkfz-heidelberg.de. ·BMC Med · Pubmed #30126408.

ABSTRACT: BACKGROUND: The prognosis of pancreatic cancer (PaC) strongly varies across different stages and age groups, which has unfortunately not been well recorded in the literature. This international population-based study aimed to provide tumor-node-metastasis (TNM) stage- and age-specific survival estimates and trends in resected and overall (resected and unresected) PaC in the early twenty-first century. METHODS: Using data from the US Surveillance, Epidemiology, and End Results-18 Program and the national cancer registries of the Netherlands, Belgium, Norway, and Slovenia, short-term and long-term overall survival results stratified by TNM stage and age in resected and overall primary PaC, irrespective of being microscopically confirmed or not, in 2003-2014 were computed using the Kaplan-Meier method. The temporal survival trends over three predefined periods (2003-2005, 2006-2008, and 2009-2011) were further examined using the log-rank test. RESULTS: In total, data for 125,183 patients were analyzed. Overall, age-stratified 3-year survival was 20-34% (< 60 years), 14-25% (60-69 years), and 9-13% (≥ 70 years) in stages I-II PaC; and 2-5% (< 60 years), 1-2% (60-69 years), and < 1-1% (≥ 70 years) in stages III-IV cancer. Patients who underwent operation had higher 3-year survival in each stage and age group (stages I-II: 23-39% (< 60 years), 16-31% (60-69 years), and 17-30% (≥ 70 years); stages III-IV: 5-19% (< 70 years) and 2-14% (≥ 70 years)). Perioperative survival also decreased with advancing stage and older age (stages I-II: 98-100% (< 60 years), 97-99% (60-69 years), and 94-99% (≥ 70 years); stages III-IV: 94-99% (< 70 years) and 81-96% (≥ 70 years)). Between 2003 and 2005 and 2009-2011, for overall PaC, both short-term and long-term survival improvements were observed in all countries except Belgium; for resected disease, short-term improvements were present only in the USA and Slovenia, but long-term improvements were observed in all countries except Slovenia, with stage-specific variations. CONCLUSIONS: Our large international study provides TNM stage- and age-specific population-based survival in overall and resected PaC that will facilitate clinical counseling. While the survival expectations for patients with resected PaC are substantially higher than the widely available and known dismal survival predictions for overall patients, conclusions on the benefits of resection cannot be made from this observational study. Patients with advanced-stage disease and/or older age should undergo careful risk assessment before treatment. Limited but inspiring improvement in survival is observed.

6 Article Nonsurgical therapies for resected and unresected pancreatic cancer in Europe and USA in 2003-2014: a large international population-based study. 2018

Huang, Lei / Jansen, Lina / Balavarca, Yesilda / van der Geest, Lydia / Lemmens, Valery / Van Eycken, Liesbet / De Schutter, Harlinde / Johannesen, Tom B / Primic-Žakelj, Maja / Zadnik, Vesna / Mägi, Margit / Pulte, Dianne / Schrotz-King, Petra / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany. · German Cancer Consortium (DKTK), 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. · Netherlands Cancer Registry (NCR), The Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands. · Belgian Cancer Registry (BCR), Brussels, Belgium. · Registry Department, The Cancer Registry of Norway (CRN), Oslo, Norway. · Epidemiology and Cancer Registry, Institute of Oncology Ljubljana, Ljubljana, Slovenia. · Estonian Cancer Registry, National Institute for Health Development, Tallinn, Estonia. ·Int J Cancer · Pubmed #29923613.

ABSTRACT: The role of chemotherapy in the treatment of pancreatic cancer (PaC) has been well-established, while radiation plays ambiguous roles. This international large-scale population-based study aimed to investigate the real-world application of chemotherapy and radiotherapy for resected and unresected PaC in Europe and USA. Population-based data from multiple European national cancer registries and the US Surveillance, Epidemiology and End Results (SEER)-18 database during 2003-2014 were analyzed. Temporal trends and geographical variations in the application rates of chemotherapy and radiotherapy were quantified using age standardization. Associations of treatment with demographic and clinical characteristics were assessed using multivariable logistic regression. A total of 141,533 PaC patients were analyzed. From 2003-2005 to 2012-2014, chemotherapy administration rates increased in most countries and more strongly among resected patients, while radiation rates were generally low with a slight decline or no obvious trend. In 2012-2014, 12.5% (Estonia) to 61.7% (Belgium) of resected and 17.1% (Slovenia) to 56.9% (Belgium) of unresected patients received chemotherapy. Radiation was administered in 2.6% (Netherlands) to 32.6% (USA) of resected and 1.0% (USA) to 6.0% (Belgium) of unresected patients. Strong temporal and geographical variations were observed. Patterns and strengths of associations of treatment administration with various demographic and clinical factors differed substantially between resected and unresected cancers and varied greatly across countries. Conclusively, administration of chemotherapy but not radiotherapy for PaC increased during the last decade in Europe and USA. Treatment rates were low and the uptake strongly varied across countries, highlighting the need for standardization in PaC treatment to improve patient care.

7 Article Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. 2018

Klein, Alison P / Wolpin, Brian M / Risch, Harvey A / Stolzenberg-Solomon, Rachael Z / Mocci, Evelina / Zhang, Mingfeng / Canzian, Federico / Childs, Erica J / Hoskins, Jason W / Jermusyk, Ashley / Zhong, Jun / Chen, Fei / Albanes, Demetrius / Andreotti, Gabriella / Arslan, Alan A / Babic, Ana / Bamlet, William R / Beane-Freeman, Laura / Berndt, Sonja I / Blackford, Amanda / Borges, Michael / Borgida, Ayelet / Bracci, Paige M / Brais, Lauren / Brennan, Paul / Brenner, Hermann / Bueno-de-Mesquita, Bas / Buring, Julie / Campa, Daniele / Capurso, Gabriele / Cavestro, Giulia Martina / Chaffee, Kari G / Chung, Charles C / Cleary, Sean / Cotterchio, Michelle / Dijk, Frederike / Duell, Eric J / Foretova, Lenka / Fuchs, Charles / Funel, Niccola / Gallinger, Steven / M Gaziano, J Michael / Gazouli, Maria / Giles, Graham G / Giovannucci, Edward / Goggins, Michael / Goodman, Gary E / Goodman, Phyllis J / Hackert, Thilo / Haiman, Christopher / Hartge, Patricia / Hasan, Manal / Hegyi, Peter / Helzlsouer, Kathy J / Herman, Joseph / Holcatova, Ivana / Holly, Elizabeth A / Hoover, Robert / Hung, Rayjean J / Jacobs, Eric J / Jamroziak, Krzysztof / Janout, Vladimir / Kaaks, Rudolf / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Kooperberg, Charles / Kulke, Matthew H / Kupcinskas, Juozas / Kurtz, Robert J / Laheru, Daniel / Landi, Stefano / Lawlor, Rita T / Lee, I-Min / LeMarchand, Loic / Lu, Lingeng / Malats, Núria / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Mohelníková-Duchoňová, Beatrice / Neale, Rachel E / Neoptolemos, John P / Oberg, Ann L / Olson, Sara H / Orlow, Irene / Pasquali, Claudio / Patel, Alpa V / Peters, Ulrike / Pezzilli, Raffaele / Porta, Miquel / Real, Francisco X / Rothman, Nathaniel / Scelo, Ghislaine / Sesso, Howard D / Severi, Gianluca / Shu, Xiao-Ou / Silverman, Debra / Smith, Jill P / Soucek, Pavel / Sund, Malin / Talar-Wojnarowska, Renata / Tavano, Francesca / Thornquist, Mark D / Tobias, Geoffrey S / Van Den Eeden, Stephen K / Vashist, Yogesh / Visvanathan, Kala / Vodicka, Pavel / Wactawski-Wende, Jean / Wang, Zhaoming / Wentzensen, Nicolas / White, Emily / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Zheng, Wei / Kraft, Peter / Li, Donghui / Chanock, Stephen / Obazee, Ofure / Petersen, Gloria M / Amundadottir, Laufey T. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. aklein1@jhmi.edu. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. aklein1@jhmi.edu. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, 06520, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, 10016, USA. · Department of Population Health, New York University School of Medicine, New York, NY, 10016, USA. · Department of Environmental Medicine, New York University School of Medicine, New York, NY, 10016, USA. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, 55905, USA. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD, 21287, USA. · Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, M5G 1×5, Canada. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, 94158, USA. · International Agency for Research on Cancer (IARC), 69372, Lyon, France. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · Division of Preventive Oncology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · National Center for Tumor Diseases (NCT), 69120, Heidelberg, Germany. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), 3720 BA, Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, 3584 CX, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, SW7 2AZ, UK. · Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. · Department of Biology, University of Pisa, 56126, Pisa, Italy. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, 00185, Rome, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. · Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA. · Cancer Care Ontario, University of Toronto, Toronto, Ontario, M5G 2L7, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, M5T 3M7, Canada. · Department of Pathology, Academic Medical Center, University of Amsterdam, 1007 MB, Amsterdam, The Netherlands. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, 08908, Spain. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 65653, Brno, Czech Republic. · Yale Cancer Center, New Haven, CT, 06510, USA. · Department of Translational Research and The New Technologies in Medicine and Surgery, University of Pisa, 56126, Pisa, Italy. · Division of Aging, Brigham and Women's Hospital, Boston, MA, 02115, USA. · Boston VA Healthcare System, Boston, MA, 02132, USA. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, 106 79, Athens, Greece. · Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, VIC, 3004, Australia. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, 3010, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, 3004, Australia. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. · SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. · Department of General Surgery, University Hospital Heidelberg, 69120, Heidelberg, Germany. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, USA. · Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, 77230, USA. · First Department of Medicine, University of Szeged, 6725, Szeged, Hungary. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. · Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. · Institute of Public Health and Preventive Medicine, Charles University, 2nd Faculty of Medicine, 150 06, Prague 5, Czech Republic. · Epidemiology Research Program, American Cancer Society, Atlanta, GA, 30303, USA. · Department of Hematology, Institute of Hematology and Transfusion Medicine, 02-776, Warsaw, Poland. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, 701 03, Ostrava, Czech Republic. · Faculty of Medicine, University of Olomouc, 771 47, Olomouc, Czech Republic. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany. · School of Clinical Medicine, University of Cambridge, Cambridge, CB2 0SP, UK. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. · ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), 08003, Barcelona, Spain. · CIBER Epidemiología y Salud Pública (CIBERESP), 08003, Barcelona, Spain. · Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, 08003, Barcelona, Spain. · Universitat Pompeu Fabra (UPF), 08002, Barcelona, Spain. · Department of Gastroenterology, Lithuanian University of Health Sciences, 44307, Kaunas, Lithuania. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, 37134, Verona, Italy. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA. · Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), 28029, Madrid, Spain. · CIBERONC, 28029, Madrid, Spain. · Oncology Department, ASL1 Massa Carrara, Carrara, 54033, Italy. · Department of Public Health Solutions, National Institute for Health and Welfare, 00271, Helsinki, Finland. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital, 775 20, Olomouc, Czech Republic. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, 4029, Australia. · Department of General Surgery, University of Heidelburg, Heidelberg, Germany. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. · Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padua, 35124, Padua, Italy. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, 40138, Bologna, Italy. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, 28029, Madrid, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08002, Barcelona, Spain. · Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Facultés de Medicine, Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, 94800, Villejuif, France. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA. · Department of Medicine, Georgetown University, Washington, 20057, USA. · Laboratory for Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00, Pilsen, Czech Republic. · Department of Surgical and Perioperative Sciences, Umeå University, 901 85, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, 90-647, Łodz, Poland. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", 71013, San Giovanni Rotondo, FG, Italy. · Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA. · Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, 20246, Hamburg, Germany. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 142 20, Prague 4, Czech Republic. · Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, 14214, USA. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA. · Department of Epidemiology, University of Washington, Seattle, WA, 98195, USA. · Perlmutter Cancer Center, New York University School of Medicine, New York, NY, 10016, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, MA, 02115, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. amundadottirl@mail.nih.gov. ·Nat Commun · Pubmed #29422604.

ABSTRACT: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10

8 Article Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation. 2018

Campa, Daniele / Pastore, Manuela / Capurso, Gabriele / Hackert, Thilo / Di Leo, Milena / Izbicki, Jakob R / Khaw, Kay-Tee / Gioffreda, Domenica / Kupcinskas, Juozas / Pasquali, Claudio / Macinga, Peter / Kaaks, Rudolf / Stigliano, Serena / Peeters, Petra H / Key, Timothy J / Talar-Wojnarowska, Renata / Vodicka, Pavel / Valente, Roberto / Vashist, Yogesh K / Salvia, Roberto / Papaconstantinou, Ioannis / Shimizu, Yasuhiro / Valsuani, Chiara / Zambon, Carlo Federico / Gazouli, Maria / Valantiene, Irena / Niesen, Willem / Mohelnikova-Duchonova, Beatrice / Hara, Kazuo / Soucek, Pavel / Malecka-Panas, Ewa / Bueno-de-Mesquita, H B As / Johnson, Theron / Brenner, Herman / Tavano, Francesca / Fogar, Paola / Ito, Hidemi / Sperti, Cosimo / Butterbach, Katja / Latiano, Anna / Andriulli, Angelo / Cavestro, Giulia Martina / Busch, Olivier R C / Dijk, Frederike / Greenhalf, William / Matsuo, Keitaro / Lombardo, Carlo / Strobel, Oliver / König, Anna-Katharina / Cuk, Katarina / Strothmann, Hendrik / Katzke, Verena / Cantore, Maurizio / Mambrini, Andrea / Oliverius, Martin / Pezzilli, Raffaele / Landi, Stefano / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Digestive and Liver Disease Unit, S. Andrea Hospital 'Sapienza' University of Rome, Rome, Italy. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Clinical Gerontology Unit, Addenbrooke's Hospital, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. · Division of Gastroenterology and Research Laboratory, Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. · Institute of Experimental Medicine, Czech Academy of Sciences and Institute of Clinical and Experimental Medicine, Prague, Czech Republic. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Visceral Surgery, Kantonsspital Aarau AG, Aarau, Switzerland. · Department of Surgery, Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy. · Second Department of Surgery, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. · Oncological Department, Azienda USL Toscana Nord Ovest, Oncological Unit of Massa Carrara, Carrara, Massa and Carrara, Italy. · Department of Medicine (DIMED), University of Padova, Padova, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment, Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, St Mary's Campus, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Division of Clinical Epidemiology, 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. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan. · Department of Surgery, Academic Medical Centre, Amsterdam, the Netherlands. · Department of Pathology, Academic Medical Centre, Amsterdam, the Netherlands. · Institute for Health Research, Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Division of General and Transplant Surgery, University of Pisa, Pisa, Italy. · Dipartimento di Ricerca Traslazionale e delle Nuove Tecnologie in Medicina e Chirurgia, University of Pisa, Pisa, Italy. · Transplant Surgery Department, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine Sant'Orsola-Malpighi Hospital, Bologna, Italy. ·Int J Cancer · Pubmed #28913878.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (OR

9 Article Immortal time bias in pharmacoepidemiological studies on cancer patient survival: empirical illustration for beta-blocker use in four cancers with different prognosis. 2017

Weberpals, Janick / Jansen, Lina / van Herk-Sukel, Myrthe P P / Kuiper, Josephina G / Aarts, Mieke J / Vissers, Pauline A J / Brenner, Hermann. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. · PHARMO Institute for Drug Outcomes Research, Utrecht, The Netherlands. · Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. h.brenner@dkfz.de. · Division of Preventive Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz.de. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz.de. ·Eur J Epidemiol · Pubmed #28864947.

ABSTRACT: Immortal time bias (ITB) is still seen frequently in medical literature. However, not much is known about this bias in the field of cancer (pharmaco-)epidemiology. In context of a hypothetical beneficial beta-blocker use among cancer patients, we aimed to demonstrate the magnitude of ITB among 9876 prostate, colorectal, lung and pancreatic cancer patients diagnosed between 1998 and 2011, which were selected from a database linkage of the Netherlands Cancer Registry and the PHARMO Database Network. Hazard ratios (HR) and 95% confidence intervals from three ITB scenarios, defining exposure at a defined point after diagnosis (model 1), at any point after diagnosis (model 2) and as multiple exposures after diagnosis (model 3), were calculated to investigate the association between beta-blockers and cancer prognosis using Cox proportional hazards regression. Results were compared to unbiased estimates derived from the Mantel-Byar model. Ignoring ITB led to substantial smaller HRs for beta-blocker use proposing a significant protective association in all cancer types [e.g. HR 0.18 (0.07-0.43) for pancreatic cancer in model 1], whereas estimates derived from the Mantel-Byar model were mainly suggesting no association [e.g. HR 1.10 (0.84-1.44)]. The magnitude of bias was consistently larger among cancer types with worse prognosis [overall median HR differences between all scenarios in model 1 and Mantel-Byar model of 0.56 (prostate), 0.72 (colorectal), 0.77 (lung) and 0.85 (pancreas)]. In conclusion, ITB led to spurious beneficial associations of beta-blocker use among cancer patients. The magnitude of ITB depends on the duration of excluded immortal time and the prognosis of each cancer.

10 Article Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21. 2016

Zhang, Mingfeng / Wang, Zhaoming / Obazee, Ofure / Jia, Jinping / Childs, Erica J / Hoskins, Jason / Figlioli, Gisella / Mocci, Evelina / Collins, Irene / Chung, Charles C / Hautman, Christopher / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Buring, Julie / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goodman, Gary E / Goodman, Phyllis J / Kamineni, Aruna / Kolonel, Laurence N / Kulke, Matthew H / Malats, Núria / Olson, Sara H / Sesso, Howard D / Visvanathan, Kala / White, Emily / Zheng, Wei / Abnet, Christian C / Albanes, Demetrius / Andreotti, Gabriella / Brais, Lauren / Bueno-de-Mesquita, H Bas / Basso, Daniela / Berndt, Sonja I / Boutron-Ruault, Marie-Christine / Bijlsma, Maarten F / Brenner, Hermann / Burdette, Laurie / Campa, Daniele / Caporaso, Neil E / Capurso, Gabriele / Cavestro, Giulia Martina / Cotterchio, Michelle / Costello, Eithne / Elena, Joanne / Boggi, Ugo / Gaziano, J Michael / Gazouli, Maria / Giovannucci, Edward L / Goggins, Michael / Gross, Myron / Haiman, Christopher A / Hassan, Manal / Helzlsouer, Kathy J / Hu, Nan / Hunter, David J / Iskierka-Jazdzewska, Elzbieta / Jenab, Mazda / Kaaks, Rudolf / Key, Timothy J / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Krogh, Vittorio / Kupcinskas, Juozas / Kurtz, Robert C / Landi, Maria T / Landi, Stefano / Le Marchand, Loic / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Neale, Rachel E / Oberg, Ann L / Panico, Salvatore / Patel, Alpa V / Peeters, Petra H M / Peters, Ulrike / Pezzilli, Raffaele / Porta, Miquel / Purdue, Mark / Quiros, J Ramón / Riboli, Elio / Rothman, Nathaniel / Scarpa, Aldo / Scelo, Ghislaine / Shu, Xiao-Ou / Silverman, Debra T / Soucek, Pavel / Strobel, Oliver / Sund, Malin / Małecka-Panas, Ewa / Taylor, Philip R / Tavano, Francesca / Travis, Ruth C / Thornquist, Mark / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vashist, Yogesh / Vodicka, Pavel / Wactawski-Wende, Jean / Wentzensen, Nicolas / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Kooperberg, Charles / Risch, Harvey A / Jacobs, Eric J / Li, Donghui / Fuchs, Charles / Hoover, Robert / Hartge, Patricia / Chanock, Stephen J / Petersen, Gloria M / Stolzenberg-Solomon, Rachael S / Wolpin, Brian M / Kraft, Peter / Klein, Alison P / Canzian, Federico / Amundadottir, Laufey T. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA. · Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Oncology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA. · Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. · New York University Cancer Institute, New York, New York, USA,. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA. · Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain. · Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Group Health Research Institute, Seattle, Washington, USA,. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Genetic and Molecular Epidemiology Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. · Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Division of Epidemiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy,. · Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, F-94805, Villejuif, France. · University Paris Sud, UMRS 1018, F-94805, Villejuif, France. · IGR, F-94805, Villejuif, France. · Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · 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. · Department of Biology, University of Pisa, Pisa, Italy. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Prevention and Cancer Control, Cancer Care Ontario, Toronto, Ontario, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · Massachusetts Veteran's Epidemiology, Research, and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. · Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Pathology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Department of Medicine, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Department of Oncology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. · Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA. · Preventive Medicine, University of Southern California, Los Angeles, California, USA. · Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. · Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Harvard School of Public Health, Boston, Massachusetts, USA. · Harvard Medical School, Boston, Massachusetts, USA. · Department of Hematology, Medical University of Łodz, Łodz, Poland. · International Agency for Research on Cancer (IARC), Lyon, France. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. · School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA. · Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Spain. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. · National School of Public Health, Athens, Greece. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland. · Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Dipartimento di Medicina Clinica E Chirurgia, Federico II Univeristy, Naples, Italy. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · Public Health and Participation Directorate, Asturias, Spain. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Surgical and Peroperative Sciences, Umeå University, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. · Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. · Hellenic Health Foundation, Athens, Greece. · Department of General, Visceral and Thoracic Surgery, University Hamburg-Eppendorf, Hamburg, Germany. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic. · Department of Social and Preventive Medicine, University at Buffalo, Buffalo, New York, USA. · New York University Cancer Institute, New York, New York, USA. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA,. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Epidemiology, the Bloomberg School of Public Health, Baltimore, Maryland, USA. ·Oncotarget · Pubmed #27579533.

ABSTRACT: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

11 Article Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium. 2016

Ordóñez-Mena, José Manuel / Schöttker, Ben / Mons, Ute / Jenab, Mazda / Freisling, Heinz / Bueno-de-Mesquita, Bas / O'Doherty, Mark G / Scott, Angela / Kee, Frank / Stricker, Bruno H / Hofman, Albert / de Keyser, Catherine E / Ruiter, Rikje / Söderberg, Stefan / Jousilahti, Pekka / Kuulasmaa, Kari / Freedman, Neal D / Wilsgaard, Tom / de Groot, Lisette Cpgm / Kampman, Ellen / Håkansson, Niclas / Orsini, Nicola / Wolk, Alicja / Nilsson, Lena Maria / Tjønneland, Anne / Pająk, Andrzej / Malyutina, Sofia / Kubínová, Růžena / Tamosiunas, Abdonas / Bobak, Martin / Katsoulis, Michail / Orfanos, Philippos / Boffetta, Paolo / Trichopoulou, Antonia / Brenner, Hermann / Anonymous14930863. ·Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120, Heidelberg, Germany. · International Agency for Research on Cancer (IARC), Lyon, France. · Department of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. · Division of Epidemiology and Biostatistics, the School of Public Health, Imperial College London, London, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · UKCRC Centre of Excellence for Public Health, Queens University of Belfast, Belfast, UK. · Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands. · Department of Public Health and Clinical Medicine, Cardiology, and Heart Center, Umeå University, Umeå, Sweden. · National Institute for Health and Welfare (THL), Helsinki, Finland. · Nutritional Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Rockville, MD, USA. · Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway. · Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. · Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · Nutritional Research, Department of Public Health and Clinical Medicine, and Arcum, Arctic Research Centre at Umeå University, Umeå, Sweden. · Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. · Jagiellonian University Medical College, Faculty of Health Sciences, Krakow, Poland. · Institute of Internal and Preventive Medicine, Novosibirsk, Russia. · National Institute of Public Health, Prague, Czech Republic. · Institute of Cardiology of Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department Epidemiology and Public Health, University College London, London, UK. · Hellenic Health Foundation, Athens, Greece. · University of Athens, Medical School, Department of Hygiene, Epidemiology and Medical Statistics, Athens, Greece. · Institute for Translational Epidemiology and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Network Aging Research (NAR), Heidelberg University, Heidelberg, Germany. h.brenner@dkfz.de. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, D-69120, Heidelberg, Germany. h.brenner@dkfz.de. · German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz.de. · Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. h.brenner@dkfz.de. ·BMC Med · Pubmed #27044418.

ABSTRACT: BACKGROUND: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality. METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs. RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking. CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.

12 Article Association of helicobacter pylori infection and chronic atrophic gastritis with risk of colonic, pancreatic and gastric cancer: A ten-year follow-up of the ESTHER cohort study. 2016

Chen, Xin-Zu / Schöttker, Ben / Castro, Felipe Andres / Chen, Hongda / Zhang, Yan / Holleczek, Bernd / Brenner, Hermann. ·Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Saarland Cancer Registry, Saarbrücken, Germany. · German Cancer Consortium (DKTK), Heidelberg, Germany. ·Oncotarget · Pubmed #26958813.

ABSTRACT: OBJECTIVES: To assess the association of H. pylori and chronic atrophic gastritis (AG) with colonic, pancreatic and gastric cancer in a population-based prospective cohort. METHODS: Serum antibodies against H. pylori in general and specific to cytotoxin-associated gene A (CagA), as well as serum pepsinogen I and II were analyzed in 9,506 men and women, aged 50-75 years in a cohort study from Saarland, Germany. Incident cases of colonic, pancreatic and gastric cancer were ascertained by record linkage with data from the Saarland Cancer Registry. RESULTS: During an average follow-up of 10.6 years, 108 colonic, 46 pancreatic and 27 gastric incident cancers were recorded. There was no association between H. pylori infection and colonic cancer (HR = 1.07; 95% CI 0.73-1.56) or pancreatic cancer (HR = 1.32; 0.73-2.39), regardless of either CagA seropositivity or AG status. In contrast, CagA+ infection was associated with a strongly increased risk of gastric cancer, especially non-cardia gastric cancer, and this association was particularly pronounced in the presence of AG. Compared to people without AG and without CagA+ infection, people with both risk factors had a significantly increased risk of non-cardia gastric cancer (HR = 32.4; 7.6-137.6). CONCLUSIONS: This large cohort study did not observe an association of H. pylori infection or AG with colonic or pancreatic cancer, but underlines that the vast majority of non-cardia gastric cancers arise from AG and infection with CagA+ H. pylori strains.

13 Article Recent Trends in Survival of Patients With Pancreatic Cancer in Germany and the United States. 2016

Sirri, Eunice / Castro, Felipe Andres / Kieschke, Joachim / Jansen, Lina / Emrich, Katharina / Gondos, Adam / Holleczek, Bernd / Katalinic, Alexander / Urbschat, Iris / Vohmann, Claudia / Brenner, Hermann. ·From the *Lower Saxony Cancer Registry, Oldenburg; †Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg; ‡Cancer Registry of Rhineland-Palatinate, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg University Mainz, Mainz; §Saarland Cancer Registry, Saarbrücken; ∥Cancer Registry of Schleswig-Holstein, Lübeck; and ¶Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT); and #German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Pancreas · Pubmed #26745860.

ABSTRACT: OBJECTIVES: Survival improvement for pancreatic cancer has not been observed in the last 4 decades. We report the most up-to-date population-based relative survival (RS) estimates and recent trends in Germany and the United States. METHODS: Data for patients diagnosed in 1997 to 2010 and followed up to 2010 were drawn from 12 population-based German cancer registries and the US SEER (Surveillance, Epidemiology and End Results) 13 registries database. Using period analysis, 5-year RS for 2007 to 2010 was derived. Model-based period analysis was used to assess 5-year RS time trends, 2002-2010. RESULTS: In total 28,977 (Germany) and 34,793 (United States) patients aged 15 to 74 years were analyzed. Five-year RS was 10.7% and 10.3% in Germany and the United States, respectively, and strongly decreased with age and tumor spread. Prognosis slightly improved from the period 2002-2004 to 2008-2010 (overall age-adjusted RS: +2.5% units in Germany and +3.4% units in the United States); improvement was particularly strong for regional stage and head and body subsites in Germany and for localized and regional stages and tail subsite in the United States. CONCLUSIONS: Although pancreatic cancer survival continues to be poor for advanced-stage patients, our study disclosed encouraging indications of first improvements in 5-year RS after decades of stagnation.

14 Article Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1. 2015

Cheng, Timothy H T / Thompson, Deborah / Painter, Jodie / O'Mara, Tracy / Gorman, Maggie / Martin, Lynn / Palles, Claire / Jones, Angela / Buchanan, Daniel D / Win, Aung Ko / Hopper, John / Jenkins, Mark / Lindor, Noralane M / Newcomb, Polly A / Gallinger, Steve / Conti, David / Schumacher, Fred / Casey, Graham / Giles, Graham G / Pharoah, Paul / Peto, Julian / Cox, Angela / Swerdlow, Anthony / Couch, Fergus / Cunningham, Julie M / Goode, Ellen L / Winham, Stacey J / Lambrechts, Diether / Fasching, Peter / Burwinkel, Barbara / Brenner, Hermann / Brauch, Hiltrud / Chang-Claude, Jenny / Salvesen, Helga B / Kristensen, Vessela / Darabi, Hatef / Li, Jingmei / Liu, Tao / Lindblom, Annika / Hall, Per / de Polanco, Magdalena Echeverry / Sans, Monica / Carracedo, Angel / Castellvi-Bel, Sergi / Rojas-Martinez, Augusto / Aguiar Jnr, Samuel / Teixeira, Manuel R / Dunning, Alison M / Dennis, Joe / Otton, Geoffrey / Proietto, Tony / Holliday, Elizabeth / Attia, John / Ashton, Katie / Scott, Rodney J / McEvoy, Mark / Dowdy, Sean C / Fridley, Brooke L / Werner, Henrica M J / Trovik, Jone / Njolstad, Tormund S / Tham, Emma / Mints, Miriam / Runnebaum, Ingo / Hillemanns, Peter / Dörk, Thilo / Amant, Frederic / Schrauwen, Stefanie / Hein, Alexander / Beckmann, Matthias W / Ekici, Arif / Czene, Kamila / Meindl, Alfons / Bolla, Manjeet K / Michailidou, Kyriaki / Tyrer, Jonathan P / Wang, Qin / Ahmed, Shahana / Healey, Catherine S / Shah, Mitul / Annibali, Daniela / Depreeuw, Jeroen / Al-Tassan, Nada A / Harris, Rebecca / Meyer, Brian F / Whiffin, Nicola / Hosking, Fay J / Kinnersley, Ben / Farrington, Susan M / Timofeeva, Maria / Tenesa, Albert / Campbell, Harry / Haile, Robert W / Hodgson, Shirley / Carvajal-Carmona, Luis / Cheadle, Jeremy P / Easton, Douglas / Dunlop, Malcolm / Houlston, Richard / Spurdle, Amanda / Tomlinson, Ian. ·Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. · Centre for Cancer Genetic Epidemiology, Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. · The Molecular Cancer Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia. · Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Victoria, Australia. · Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia. · Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA. · Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada. · Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA. · Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia. · Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. · London School of Hygiene and Tropical Medicine, London, UK. · Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, UK. · Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK and 17 Division of Breast Cancer Research, Institute of Cancer Research, London, UK. · Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. · Department of Oncology, KU Leuven, Belgium. · University of California at Los Angeles, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, Los Angeles, CA, USA. · Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. · Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany. · Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, University of Tuebingen, Germany. · Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Norway. · Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Oncology, Division of Medicine, Akershus University Hospital, Ahus, Norway. · Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Grupo de investigación Citogenética, Filogenia y Evolución de Poblaciones, Universidad del Tolima, Ibagué, Tolima, Colombia. · Departamento de Antropologia Biologica, Facultad de Humanidades, UDELAR, Magallanes 1577, CP 11200, Montevideo, Uruguay. · Universidade de Santiago de Compostel, R/ San Francisco s/n 15782, Santiago de Compostela, Spain. · Genetic Predisposition to Colorectal Cancer Group, Gastrointestinal &Pancreatic Oncology Team, IDIBAPS/CIBERehd/Hospital Clínic, Centre Esther Koplowitz (CEK), Rosselló 153 planta 4, 08036 Barcelona, Spain. · Universidad Autónoma De Nuevo León, Pedro de Alba s/n, San Nicolás de Los Garza, Nuevo León, Mexico. · Hospital A.C. Camargo, São Paulo, Brazil. · Department of Genetics and IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal, and Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal. · School of Medicine and Public Health, University of Newcastle, NSW, Australia. · Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia. · Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, NSW, Australia. · Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA. · Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA. · Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Norway. · Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany. · Hannover Medical School, Clinics of Gynaecology and Obstetrics, Hannover, Germany. · Hannover Medical School, Gynaecology Research Unit, Hannover, Germany. · Division of Gynaecological Oncology, University Hospital Leuven, Leuven, Belgium. · Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. · Department of Obstetrics and Gynecology, Division of Tumor Genetics, Technical University of Munich, Munich, Germany. · Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals, KU Leuven, University of Leuven, 3000, Belgium. · Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O.Box 3354, Riyadh11211, Saudi Arabia. · Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. · Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK. · Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK. · The Roslin Institute, University of Edinburgh, Easter Bush, Roslin, EH25 9RG, UK. · Centre for Population Health Sciences, University of Edinburgh, Edinburgh, EH8 9AG, UK. · Stanford Cancer Institute, Lorry Lokey Building/SIM 1, 265 Campus Drive, Ste G2103, Stanford, CA 94305-5456, USA. · Department of Cancer Genetics, St. George's University of London, London SW17 0RE, UK. · Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA. · Oxford NIHR Comprehensive Biomedical Research Centre, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK. ·Sci Rep · Pubmed #26621817.

ABSTRACT: High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10(-9)) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10(-8)), with the alleles showing opposite effects on the risks of the two cancers.

15 Article Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer. 2015

Childs, Erica J / Mocci, Evelina / Campa, Daniele / Bracci, Paige M / Gallinger, Steven / Goggins, Michael / Li, Donghui / Neale, Rachel E / Olson, Sara H / Scelo, Ghislaine / Amundadottir, Laufey T / Bamlet, William R / Bijlsma, Maarten F / Blackford, Amanda / Borges, Michael / Brennan, Paul / Brenner, Hermann / Bueno-de-Mesquita, H Bas / Canzian, Federico / Capurso, Gabriele / Cavestro, Giulia M / Chaffee, Kari G / Chanock, Stephen J / Cleary, Sean P / Cotterchio, Michelle / Foretova, Lenka / Fuchs, Charles / Funel, Niccola / Gazouli, Maria / Hassan, Manal / Herman, Joseph M / Holcatova, Ivana / Holly, Elizabeth A / Hoover, Robert N / Hung, Rayjean J / Janout, Vladimir / Key, Timothy J / Kupcinskas, Juozas / Kurtz, Robert C / Landi, Stefano / Lu, Lingeng / Malecka-Panas, Ewa / Mambrini, Andrea / Mohelnikova-Duchonova, Beatrice / Neoptolemos, John P / Oberg, Ann L / Orlow, Irene / Pasquali, Claudio / Pezzilli, Raffaele / Rizzato, Cosmeri / Saldia, Amethyst / Scarpa, Aldo / Stolzenberg-Solomon, Rachael Z / Strobel, Oliver / Tavano, Francesca / Vashist, Yogesh K / Vodicka, Pavel / Wolpin, Brian M / Yu, Herbert / Petersen, Gloria M / Risch, Harvey A / Klein, Alison P. ·Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. · 1] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2] Department of Biology, University of Pisa, Pisa, Italy. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. · Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of Population Health, QIMR Berghofer Medical Research Institute, Kelvin Grove,Queensland, Australia. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · International Agency for Research on Cancer (IARC), Lyon, France. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany. · 1] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. [2] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. [3] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [4] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy. · Università Vita Salute San Raffaele and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy. · 1] Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada. [2] Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada. · 1] Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada. [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and Medical Faculty Masaryk University, Brno, Czech Republic. · 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · Department of Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Department of Radiation Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic. · Cancer Epidemiology Unit, University of Oxford, Oxford, UK. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Department of Biology, Section of Genetics, University of Pisa, Pisa, Italy. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Oncology, Azienda USL 1 Massa Carrara, Massa Carrara, Italy. · Laboratory of Toxicogenomics, Institute of Public Health, Prague, Czech Republic. · National Institute for Health Research (NIHR) Pancreas Biomedical Research Unit, Liverpool Clinical Trials Unit and Cancer Research UK Clinical Trials Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Department of Surgery, Gastroenterology and Oncology, University of Padua, Padua, Italy. · Pancreas Unit, Department of Digestive Diseases, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · ARC-NET-Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Rockville, Maryland, USA. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences, Prague, Czech Republic. · 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA. · 1] Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. [2] Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. ·Nat Genet · Pubmed #26098869.

ABSTRACT: Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

16 Article TERT gene harbors multiple variants associated with pancreatic cancer susceptibility. 2015

Campa, Daniele / Rizzato, Cosmeri / Stolzenberg-Solomon, Rachael / Pacetti, Paola / Vodicka, Pavel / Cleary, Sean P / Capurso, Gabriele / Bueno-de-Mesquita, H B As / Werner, Jens / Gazouli, Maria / Butterbach, Katja / Ivanauskas, Audrius / Giese, Nathalia / Petersen, Gloria M / Fogar, Paola / Wang, Zhaoming / Bassi, Claudio / Ryska, Miroslav / Theodoropoulos, George E / Kooperberg, Charles / Li, Donghui / Greenhalf, William / Pasquali, Claudio / Hackert, Thilo / Fuchs, Charles S / Mohelnikova-Duchonova, Beatrice / Sperti, Cosimo / Funel, Niccola / Dieffenbach, Aida Karina / Wareham, Nicholas J / Buring, Julie / Holcátová, Ivana / Costello, Eithne / Zambon, Carlo-Federico / Kupcinskas, Juozas / Risch, Harvey A / Kraft, Peter / Bracci, Paige M / Pezzilli, Raffaele / Olson, Sara H / Sesso, Howard D / Hartge, Patricia / Strobel, Oliver / Małecka-Panas, Ewa / Visvanathan, Kala / Arslan, Alan A / Pedrazzoli, Sergio / Souček, Pavel / Gioffreda, Domenica / Key, Timothy J / Talar-Wojnarowska, Renata / Scarpa, Aldo / Mambrini, Andrea / Jacobs, Eric J / Jamroziak, Krzysztof / Klein, Alison / Tavano, Francesca / Bambi, Franco / Landi, Stefano / Austin, Melissa A / Vodickova, Ludmila / Brenner, Hermann / Chanock, Stephen J / Delle Fave, Gianfranco / Piepoli, Ada / Cantore, Maurizio / Zheng, Wei / Wolpin, Brian M / Amundadottir, Laufey T / Canzian, Federico. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic. · Department of Surgery, University Health Network, University of Toronto, Toronto, ON, Canada. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department of 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, 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. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Basic Medical Science, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. · Department of Laboratory Medicine, University Hospital of Padua, Padua, Italy. · Surgical and Oncological Department, Pancreas Institute - University and Hospital Trust of Verona, Verona, Italy. · Department of Surgery, Second Faculty of Medicine, Charles University in Prague and Central Military Hospital, Prague, Czech Republic. · 1st Department of Propaedeutic Surgery, School of Medicine, University of Athens, Athens, Greece. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA. · Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX. · National Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of Surgery, Gastroenterology and Oncology (DISCOG), University of Padua, Padua, Italy. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. · Department of Oncology, Palacky University Medical School and Teaching Hospital in Olomouc, Olomouc, Czech Republic. · Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy. · German Cancer Consortium (DKTK), Heidelberg, Germany. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. · Divisions of Preventive Medicine and Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. · Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padua, Padua, Italy. · 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 and Biostatistics, University of California San Francisco, San Francisco, CA. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. · Division of Epidemiology, Departments of Obstetrics and Gynecology, Environmental Medicine, and Population Health, New York University School of Medicine, New York, NY. · Surgical Clinic 4, University of Padua, Padua, Italy. · Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo Della Sofferenza,", San Giovanni Rotondo, Italy. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Epidemiology Research Program, American Cancer Society, Atlanta, GA. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Biology, University of Pisa, Pisa, Italy. · Department of Epidemiology, University of Washington, Seattle, WA. · Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN. ·Int J Cancer · Pubmed #25940397.

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.

17 Article Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk. 2015

Painter, Jodie N / O'Mara, Tracy A / Batra, Jyotsna / Cheng, Timothy / Lose, Felicity A / Dennis, Joe / Michailidou, Kyriaki / Tyrer, Jonathan P / Ahmed, Shahana / Ferguson, Kaltin / Healey, Catherine S / Kaufmann, Susanne / Hillman, Kristine M / Walpole, Carina / Moya, Leire / Pollock, Pamela / Jones, Angela / Howarth, Kimberley / Martin, Lynn / Gorman, Maggie / Hodgson, Shirley / Anonymous2970811 / Anonymous2980811 / De Polanco, Ma Magdalena Echeverry / Sans, Monica / Carracedo, Angel / Castellvi-Bel, Sergi / Rojas-Martinez, Augusto / Santos, Erika / Teixeira, Manuel R / Carvajal-Carmona, Luis / Shu, Xiao-Ou / Long, Jirong / Zheng, Wei / Xiang, Yong-Bing / Anonymous2990811 / Montgomery, Grant W / Webb, Penelope M / Scott, Rodney J / McEvoy, Mark / Attia, John / Holliday, Elizabeth / Martin, Nicholas G / Nyholt, Dale R / Henders, Anjali K / Fasching, Peter A / Hein, Alexander / Beckmann, Matthias W / Renner, Stefan P / Dörk, Thilo / Hillemanns, Peter / Dürst, Matthias / Runnebaum, Ingo / Lambrechts, Diether / Coenegrachts, Lieve / Schrauwen, Stefanie / Amant, Frederic / Winterhoff, Boris / Dowdy, Sean C / Goode, Ellen L / Teoman, Attila / Salvesen, Helga B / Trovik, Jone / Njolstad, Tormund S / Werner, Henrica M J / Ashton, Katie / Proietto, Tony / Otton, Geoffrey / Tzortzatos, Gerasimos / Mints, Miriam / Tham, Emma / Anonymous3000811 / Hall, Per / Czene, Kamila / Liu, Jianjun / Li, Jingmei / Hopper, John L / Southey, Melissa C / Anonymous3010811 / Ekici, Arif B / Ruebner, Matthias / Johnson, Nicola / Peto, Julian / Burwinkel, Barbara / Marme, Frederik / Brenner, Hermann / Dieffenbach, Aida K / Meindl, Alfons / Brauch, Hiltrud / Anonymous3020811 / Lindblom, Annika / Depreeuw, Jeroen / Moisse, Matthieu / Chang-Claude, Jenny / Rudolph, Anja / Couch, Fergus J / Olson, Janet E / Giles, Graham G / Bruinsma, Fiona / Cunningham, Julie M / Fridley, Brooke L / Børresen-Dale, Anne-Lise / Kristensen, Vessela N / Cox, Angela / Swerdlow, Anthony J / Orr, Nicholas / Bolla, Manjeet K / Wang, Qin / Weber, Rachel Palmieri / Chen, Zhihua / Shah, Mitul / French, Juliet D / Pharoah, Paul D P / Dunning, Alison M / Tomlinson, Ian / Easton, Douglas F / Edwards, Stacey L / Thompson, Deborah J / Spurdle, Amanda B. ·QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. · Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation, and School of Biomedical Science and. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care and. · Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. · Institute of Health and Biomedical Innovation and School of Biomedical Science, Queensland University of Technology, Brisbane, QLD, Australia. · Department of Clinical Genetics, St George's Hospital Medical School, London, UK. · Grupo de Investigación Citogenética, Filogenia y Evolución de Poblaciones, Universidad del Tolima, Ibagué, Tolima, Colombia. · Department of Biological Anthropology, College of Humanities and Educational Sciences, University of the Republic, Magallanes, Montevideo, Uruguay. · Grupo de Medicina Xenómica, Fundación Galega de Medicina Xenómica (SERGAS) and CIBERER, Universidade de Santiago de Compostela, Santiago de Compostela, Spain, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, KSA. · Genetic Predisposition to Colorectal Cancer Group, Gastrointestinal & Pancreatic Oncology Team, IDIBAPS/CIBERehd/Hospital Clínic, Centre Esther Koplowitz (CEK), Barcelona, Spain. · Universidad Autónoma de Nuevo León, Pedro de Alba s/n, San Nicolás de Los Garza, Nuevo León, Mexico. · Hospital A.C. Camargo, São Paulo, Brazil. · Department of Genetics, Portuguese Oncology Institute, Porto, Portugal, Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK, Grupo de Investigación Citogenética, Filogenia y Evolución de Poblaciones, Universidad del Tolima, Ibagué, Tolima, Colombia, Genome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, USA. · Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China. · Hunter Medical Research Institute and, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia, Centre for Information Based Medicine and School of Biomedical Science and Pharmacy. · Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health. · Hunter Medical Research Institute and, Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health. · Hunter Medical Research Institute and, Centre for Information Based Medicine and School of Medicine and Public Health. · Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. · University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. · Gynaecology Research Unit and. · Clinics of Gynaecology and Obstetrics, Hannover Medical School, Hannover, Germany. · Dept. of Gynaecology, Friedrich Schiller University Jena, Jena, Germany. · Vesalius Research Center, VIB, Leuven, Belgium, Department of Oncology, Laboratory for Translational Genetics. · Division of Gynaecological Oncology, Department of Oncology, University Hospital Leuven, KU Leuven, Belgium. · Division of Gynecologic Oncology, Department of Obstetrics and Gynecology. · Division of Epidemiology, Department of Health Science Research and. · Department of Clinical Science, Centre for Cancerbiomarkers, The University of Bergen, Norway, Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway. · Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia, Faculty of Health, Centre for Information Based Medicine and the Discipline of Medical Genetics, School of Biomedical Sciences and Pharmacy and. · Faculty of Health, School of Medicine and Public Health, University of Newcastle, NSW, Australia. · Department of Women's and Children's Health. · Department of Molecular Medicine and Surgery and. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. · Human Genetics, Genome Institute of Singapore, Singapore. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health and. · Department of Pathology, Genetic Epidemiology Laboratory, The University of Melbourne, Melbourne, VIC, Australia. · Institute of Human Genetics, University Hospital, Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. · Breakthrough Breast Cancer Research Centre. · London School of Hygiene and Tropical Medicine, London, UK. · Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, Molecular Epidemiology, C080. · Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. · Division of Clinical Epidemiology and Aging Research, German Cancer Consortium (DKTK), Heidelberg, Germany. · Division of Tumor Genetics, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany. · Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology Stuttgart, University of Tuebingen, Germany. · Vesalius Research Center, VIB, Leuven, Belgium. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Cancer Epidemiology/Clinical Cancer Registry and Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany. · Departments of Laboratory Medicine and Pathology, and Health Science Research, Mayo Clinic, Rochester, MN, USA. · Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health and Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, VIC, Australia, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia. · Cancer Epidemiology Centre, The Cancer Council Victoria, Melbourne, VIC, Australia. · Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA. · Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway, Faculty of Medicine, The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway, Faculty of Medicine, The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway, Division of Medicine, Department of Clinical Molecular Oncology, Akershus University Hospital, Ahus, Norway. · Department of Oncology, Sheffield Cancer Research Centre, University of Sheffield, Sheffield, UK. · Division of Genetics and Epidemiology and, Division of Breast Cancer Research, Institute of Cancer Research, London, UK. · Division of Breast Cancer Research, Institute of Cancer Research, London, UK. · Department of Community and Family Medicine, Duke University School of Medicine, Durham, NC, USA. · Division of Population Sciences, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA. · Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care and Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK. · QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia, amanda.spurdle@qimrberghofer.edu.au. ·Hum Mol Genet · Pubmed #25378557.

ABSTRACT: Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression.

18 Article Changes in survival by ethnicity of patients with cancer between 1992-1996 and 2002-2006: is the discrepancy decreasing? 2012

Pulte, D / Redaniel, M T / Brenner, H / Jeffreys, M. ·Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. pultedi@gmail.com ·Ann Oncol · Pubmed #22396445.

ABSTRACT: BACKGROUND: Patients of minority race/ethnicity have lower survival after diagnosis with most types of cancer. Little data are available concerning changes in disparity over time. Here, we examine changes in survival by race/ethnicity of patients with common cancers in two recent time periods. PATIENTS AND METHODS: We used modeled period analysis to determine relative survival (RS) for non-Hispanic white (nHw), African-American (AA), and Hispanic patients in the Surveillance, Epidemiology, and End Results database diagnosed with common solid and hematological malignancies. RESULTS: Five-year RS improved overall and for nHw for each tumor examined, ranging from + 2% points (pancreatic cancer) to + 16.4% points [non-Hodgkin's lymphoma, (NHL)]. Greater improvement was observed for AA and Hispanics than nHw in breast and prostate cancer and NHL. Less improvement was observed for AA and Hispanics than for nHw for lung and pancreatic cancer. No statistically significant improvement was observed for AA and Hispanics with myeloma or acute leukemia. Survival disparities ranging from 0.5% points (myeloma) to 13.1% points (breast) between nHw and AA remained. CONCLUSIONS: Progress has been made in decreasing disparities in survival between nHw and minorities in breast cancer, prostate cancer, and NHL. Little progress has been made in reducing disparities for the other studied cancers.