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Pancreatic Neoplasms: HELP
Articles by Paul Brennan
Based on 15 articles published since 2010
(Why 15 articles?)
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Between 2010 and 2020, P. Brennan wrote the following 15 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article Healthy lifestyle and the risk of pancreatic cancer in the EPIC study. 2019

Naudin, Sabine / Viallon, Vivian / Hashim, Dana / Freisling, Heinz / Jenab, Mazda / Weiderpass, Elisabete / Perrier, Flavie / McKenzie, Fiona / Bueno-de-Mesquita, H Bas / Olsen, Anja / Tjønneland, Anne / Dahm, Christina C / Overvad, Kim / Mancini, Francesca R / Rebours, Vinciane / Boutron-Ruault, Marie-Christine / Katzke, Verena / Kaaks, Rudolf / Bergmann, Manuela / Boeing, Heiner / Peppa, Eleni / Karakatsani, Anna / Trichopoulou, Antonia / Pala, Valeria / Masala, Giovana / Panico, Salvatore / Tumino, Rosario / Sacerdote, Carlotta / May, Anne M / van Gils, Carla H / Rylander, Charlotta / Borch, Kristin Benjaminsen / Chirlaque López, María Dolores / Sánchez, Maria-Jose / Ardanaz, Eva / Quirós, José Ramón / Amiano Exezarreta, Pilar / Sund, Malin / Drake, Isabel / Regnér, Sara / Travis, Ruth C / Wareham, Nick / Aune, Dagfinn / Riboli, Elio / Gunter, Marc J / Duell, Eric J / Brennan, Paul / Ferrari, Pietro. ·Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France. · Department of Hematology and Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Nutritional Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France. · Director Office, International Agency for Research on Cancer, World Health Organization, Lyon, France. · Environment and Radiation section, Agency for Research on Cancer, World Health Organization, Lyon, France. · Departement for Determinants of Chronic Diseases (Former), National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Gastroenterology and Hepathology, University Medical Center, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. · Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. · CESP, Faculté de médecine (USVQ), Université Paris-Sud, INSERM, Université Paris-Saclay, Villejuif, France. · Inserm UMR1018, Institut Gustave Roussy, Villejuif, France. · Pancreatology Department, Beaujon Hospital, AP-HP, Clichy, France. · Inserm UMR1149, DHU Unit, Paris-Diderot University, Paris, France. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany. · Hellenic Health Foundation, Athens, Greece. · Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, ATTIKON University Hospital of Athens, Haidari, Greece. · School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. · Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. · Department of Clinical and Experimental Medecine, University Federico II, Naples, Italy. · Cancer Registry and Histopathology Department, Civic M.P.Arezzo Hospital, Ragusa, Italy. · Unit of Cancer Epidemiology, Città della Salute e della Scienza University, Hospital and Center for Cancer Prevention (CPO), Turin, Italy. · Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain. · Spanish Consortium for Research and Public Health (CIBERESP), Madrid, Spain. · Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria, Universidad de Granada, Granada, Spain. · Navarra Public Health Institute, Pamplona, Spain. · IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Public Health Directorate, Asturias, Spain. · Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. · Department of Surgical and Preoperative Sciences, Umeå University, Umeå, Sweden. · Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. · Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom. · MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom. · Department of Nutrition, Bjørknes University College, Oslo, Norway. · Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. · Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France. · Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, World Health Organization, 150, Cours Albert Thomas, 69372, Lyon Cedex 08, France. ferrarip@iarc.fr. ·Eur J Epidemiol · Pubmed #31564045.

ABSTRACT: Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLI

2 Article Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer. 2019

Walsh, Naomi / Zhang, Han / Hyland, Paula L / Yang, Qi / Mocci, Evelina / Zhang, Mingfeng / Childs, Erica J / Collins, Irene / Wang, Zhaoming / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Brennan, Paul / Canzian, Federico / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goggins, Michael / Goodman, Gary E / Goodman, Phyllis J / Hung, Rayjean J / Kooperberg, Charles / Kurtz, Robert C / Malats, Núria / LeMarchand, Loic / Neale, Rachel E / Olson, Sara H / Scelo, Ghislaine / Shu, Xiao O / Van Den Eeden, Stephen K / Visvanathan, Kala / White, Emily / Zheng, Wei / Anonymous2461116 / Albanes, Demetrius / Andreotti, Gabriella / Babic, Ana / Bamlet, William R / Berndt, Sonja I / Borgida, Ayelet / Boutron-Ruault, Marie-Christine / Brais, Lauren / Brennan, Paul / Bueno-de-Mesquita, Bas / Buring, Julie / Chaffee, Kari G / Chanock, Stephen / Cleary, Sean / Cotterchio, Michelle / Foretova, Lenka / Fuchs, Charles / M Gaziano, J Michael / Giovannucci, Edward / Goggins, Michael / Hackert, Thilo / Haiman, Christopher / Hartge, Patricia / Hasan, Manal / Helzlsouer, Kathy J / Herman, Joseph / Holcatova, Ivana / Holly, Elizabeth A / Hoover, Robert / Hung, Rayjean J / Janout, Vladimir / Klein, Eric A / Kurtz, Robert C / Laheru, Daniel / Lee, I-Min / Lu, Lingeng / Malats, Núria / Mannisto, Satu / Milne, Roger L / Oberg, Ann L / Orlow, Irene / Patel, Alpa V / Peters, Ulrike / Porta, Miquel / Real, Francisco X / Rothman, Nathaniel / Sesso, Howard D / Severi, Gianluca / Silverman, Debra / Strobel, Oliver / Sund, Malin / Thornquist, Mark D / Tobias, Geoffrey S / Wactawski-Wende, Jean / Wareham, Nick / Weiderpass, Elisabete / Wentzensen, Nicolas / Wheeler, William / Yu, Herbert / Zeleniuch-Jacquotte, Anne / Kraft, Peter / Li, Donghui / Jacobs, Eric J / Petersen, Gloria M / Wolpin, Brian M / Risch, Harvey A / Amundadottir, Laufey T / Yu, Kai / Klein, Alison P / Stolzenberg-Solomon, Rachael Z. ·National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. · Division of Applied Regulatory Science, Office of Translational Science, Center for Drug Evaluation & Research, U.S. Food and Drug Administration, Silver Spring, MD. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD. · Division of Epidemiology II, Office of Surveillance and Epidemiology, Center for Drug Evaluation & Research, U.S. Food and Drug Administration, Silver Spring, MD. · Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee. · Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY. · Department of Environmental Medicine, New York University School of Medicine, New York, NY. · Department of Population Health, New York University School of Medicine, New York, NY. · Department of Epidemiology and Biostatistics, University of California, San Francisco, CA. · International Agency for Research on Cancer (IARC), Lyon, France. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain. · Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada. · Cancer Epidemiology and Intelligence Division, 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. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, MD. · Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA. · SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. · Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. · CIBERONC, Madrid, Spain. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI. · Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN. · Division of Research, Kaiser Permanente Northern California, Oakland, CA. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. · Department of Epidemiology, University of Washington, Seattle, WA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. · Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Facultés de Medicine, Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, Villejuif, France. · 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, UK. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA. · Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. · Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN. · Cancer Care Ontario, University of Toronto, Toronto, ON, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Yale Cancer Center, New Haven, CT. · Division of Aging, Brigham and Women's Hospital, Boston, MA. · Boston VA Healthcare System, Boston, MA. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA. · Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX. · Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD. · Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD. · Institute of Public Health and Preventive Medicine, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Czech Republic. · Faculty of Medicine, University of Olomouc, Olomouc, Czech Republic. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT. · Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland. · Epidemiology Research Program, American Cancer Society, Atlanta, GA. · CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. · Hospital del Mar Institute of Medical Research (IMIM), Universitat Autònoma de Barcelona, Barcelona, Spain. · Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre-CNIO, Madrid, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY. · MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. · Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Genetic Epidemiology Group, Folkhälsan Research Center and Faculty of Medicine, University of Helsinki, Helsinki, Finland. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Information Management Systems, Silver Spring, MD. · Perlmutter Cancer Center, New York University School of Medicine, New York, NY. · Department of Biostatistics, Harvard School of Public Health, Boston, MA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX. ·J Natl Cancer Inst · Pubmed #30541042.

ABSTRACT: BACKGROUND: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. METHODS: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. RESULTS: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. CONCLUSION: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.

3 Article CA19-9 and apolipoprotein-A2 isoforms as detection markers for pancreatic cancer: a prospective evaluation. 2019

Honda, Kazufumi / Katzke, Verena A / Hüsing, Anika / Okaya, Shinobu / Shoji, Hirokazu / Onidani, Kaoru / Olsen, Anja / Tjønneland, Anne / Overvad, Kim / Weiderpass, Elisabete / Vineis, Paolo / Muller, David / Tsilidis, Kostas / Palli, Domenico / Pala, Valeria / Tumino, Rosario / Naccarati, Alessio / Panico, Salvatore / Aleksandrova, Krasimira / Boeing, Heiner / Bueno-de-Mesquita, H Bas / Peeters, Petra H / Trichopoulou, Antonia / Lagiou, Pagona / Khaw, Kay-Tee / Wareham, Nick / Travis, Ruth C / Merino, Susana / Duell, Eric J / Rodríguez-Barranco, Miguel / Chirlaque, María Dolores / Barricarte, Aurelio / Rebours, Vinciane / Boutron-Ruault, Marie-Chiristine / Romana Mancini, Francesca / Brennan, Paul / Scelo, Ghislaine / Manjer, Jonas / Sund, Malin / Öhlund, Daniel / Canzian, Federico / Kaaks, Rudolf. ·Department of Biomarker for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan. · Japan Agency for Medical Research and Development (AMED) CREST, Tokyo, Japan. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. · Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece. · Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. · Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, Ragusa, Italy. · Department of Molecular and Genetic Epidemiology, IIGM - Italian Institute for Genomic Medicine, Torino, Italy. · Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. · Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. · 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 Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands. · MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. · Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, National and Kapodistrian University of Athens, School of Medicine, WHO Collaborating Center for Nutrition and Health. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. · Cancer Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. · MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Public Health Directorate, Asturias, Spain, Acknowledgment of funds: Regional Government of Asturias. · PanC4 Consortium, Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain. · Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. · Department of Epidemiology, Murcia Regional Health Council, CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Ronda de Levante, Murcia, Spain. · Navarra Public Health Institute, Pamplona, Spain. · IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Pancreatology Unit, Beaujon Hospital, Clichy, France. · INSERM - UMR 1149, University Paris 7, Paris, France. · CESP, INSERM U1018, Univ. Paris-Sud, UVSQ, Université Paris-Saclay, Villejuif, France. · Lifestyle, Genes and Health: Integrative Trans-Generational Epidemiology, Gustave Roussy, Villejuif, France. · Section of Genetics, International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France. · Department of Surgery, Skåne University Hospital, Lund University, Lund, Sweden. · Department of Surgical and Preoperative Sciences, Umeå University, Umeå, Sweden. · Department of Radiation Sciences and Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. · Genomic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Int J Cancer · Pubmed #30259989.

ABSTRACT: Recently, we identified unique processing patterns of apolipoprotein A2 (ApoA2) in patients with pancreatic cancer. Our study provides a first prospective evaluation of an ApoA2 isoform ("ApoA2-ATQ/AT"), alone and in combination with carbohydrate antigen 19-9 (CA19-9), as an early detection biomarker for pancreatic cancer. We performed ELISA measurements of CA19-9 and ApoA2-ATQ/AT in 156 patients with pancreatic cancer and 217 matched controls within the European EPIC cohort, using plasma samples collected up to 60 months prior to diagnosis. The detection discrimination statistics were calculated for risk scores by strata of lag-time. For CA19-9, in univariate marker analyses, C-statistics to distinguish future pancreatic cancer patients from cancer-free individuals were 0.80 for plasma taken ≤6 months before diagnosis, and 0.71 for >6-18 months; for ApoA2-ATQ/AT, C-statistics were 0.62, and 0.65, respectively. Joint models based on ApoA2-ATQ/AT plus CA19-9 significantly improved discrimination within >6-18 months (C = 0.74 vs. 0.71 for CA19-9 alone, p = 0.022) and ≤ 18 months (C = 0.75 vs. 0.74, p = 0.022). At 98% specificity, and for lag times of ≤6, >6-18 or ≤ 18 months, sensitivities were 57%, 36% and 43% for CA19-9 combined with ApoA2-ATQ/AT, respectively, vs. 50%, 29% and 36% for CA19-9 alone. Compared to CA19-9 alone, the combination of CA19-9 and ApoA2-ATQ/AT may improve detection of pancreatic cancer up to 18 months prior to diagnosis under usual care, and may provide a useful first measure for pancreatic cancer detection prior to imaging.

4 Article A Plasma-Derived Protein-Metabolite Multiplexed Panel for Early-Stage Pancreatic Cancer. 2019

Fahrmann, Johannes F / Bantis, Leonidas E / Capello, Michela / Scelo, Ghislaine / Dennison, Jennifer B / Patel, Nikul / Murage, Eunice / Vykoukal, Jody / Kundnani, Deepali L / Foretova, Lenka / Fabianova, Eleonora / Holcatova, Ivana / Janout, Vladimir / Feng, Ziding / Yip-Schneider, Michele / Zhang, Jianjun / Brand, Randall / Taguchi, Ayumu / Maitra, Anirban / Brennan, Paul / Max Schmidt, C / Hanash, Samir. ·Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX. · International Agency for Research on Cancer (IARC), Lyon, France. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia. · Catholic University, Faculty of Healthy, Ružomberok, Slovakia. · Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. · Faculty of Medicine, Palacky University, Olomouc, Czech Republic. · Department Surgery, Indiana University School of Medicine, Indianapolis, IN. · Department of Epidemiology, Fairbanks School of Public Health, Indiana University, Indianapolis, IN. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX. ·J Natl Cancer Inst · Pubmed #30137376.

ABSTRACT: BACKGROUND: We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a previously validated protein panel for early-stage PDAC. METHODS: A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated. RESULTS: Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval [CI] = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19-9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02). CONCLUSIONS: A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.

5 Article Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study. 2018

Naudin, Sabine / Li, Kuanrong / Jaouen, Tristan / Assi, Nada / Kyrø, Cecilie / Tjønneland, Anne / Overvad, Kim / Boutron-Ruault, Marie-Christine / Rebours, Vinciane / Védié, Anne-Laure / Boeing, Heiner / Kaaks, Rudolf / Katzke, Verena / Bamia, Christina / Naska, Androniki / Trichopoulou, Antonia / Berrino, Franco / Tagliabue, Giovanna / Palli, Domenico / Panico, Salvatore / Tumino, Rosario / Sacerdote, Carlotta / Peeters, Petra H / Bueno-de-Mesquita, H B As / Weiderpass, Elisabete / Gram, Inger Torhild / Skeie, Guri / Chirlaque, Maria-Dolores / Rodríguez-Barranco, Miguel / Barricarte, Aurelio / Quirós, Jose Ramón / Dorronsoro, Miren / Johansson, Ingegerd / Sund, Malin / Sternby, Hanna / Bradbury, Kathryn E / Wareham, Nick / Riboli, Elio / Gunter, Marc / Brennan, Paul / Duell, Eric J / Ferrari, Pietro. ·Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer, Lyon, France. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. · CESP, INSERM U1018, University of Paris-Sud, UVSQ, University of Paris-Saclay, Villejuif, France. · Institut Gustave Roussy, Villejuif, France. · Pancreatology Unit, Beaujon Hospital, Clichy, France. · INSERM U1149, University Paris 7, Paris, France. · Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Potsdam, Germany. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Hellenic Health Foundation, Athens, Greece. · Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, WHO Collaborating Center for Nutrition and Health, National and Kapodistrian University of Athens, Athens, Greece. · Department of Preventive & Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. · Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy. · Cancer Registry and Histopathology Department, Civic M.P.Arezzo Hospital, Ragusa, Italy, Ragusa, Italy. · Unit of Cancer Epidemiology, Hospital and Center for Cancer Prevention (CPO), Città della Salute e della Scienza University, Turin, Italy. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala, Malaysia, Lumpur. · Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. · CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. · Department of Health and Social Sciences, University of Murcia, Murcia, Spain. · Biosanitary Investigation Institute (IBS) of Granada, University Hospital and University of Granada, Granada, Spain. · Navarra Public Health Institute, Pamplona, Spain. · Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. · Public Health Directorate, Asturias, Spain. · Subdirección de Salud Pública de Gipuzkoa, Gobierno Vasco, San Sebastian, Spain. · Department of Odontology, Cariology, Umeå University, Umeå, Sweden. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Department of Surgery, Institution of Clinical Sciences Malmö, Lund University, Malmö, Sweden. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom. · School of Public Health, Imperial College London, London, United Kingdom. · Nutrition and Epidemiology Group, International Agency for Research on Cancer, Lyon, France. · Genetic Epidemiology Group, International Agency for Research on Cancer, Lyon, France. · Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-Idibell), Barcelona, Spain. ·Int J Cancer · Pubmed #29524225.

ABSTRACT: Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.

6 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

7 Article Opium Use and Risk of Pancreatic Cancer: A Prospective Cohort Study. 2018

Moossavi, Shirin / Mohamadnejad, Mehdi / Pourshams, Akram / Poustchi, Hossein / Islami, Farhad / Sharafkhah, Maryam / Mirminachi, Babak / Nasseri-Moghaddam, Siavosh / Semnani, Shahryar / Shakeri, Ramin / Etemadi, Arash / Merat, Shahin / Khoshnia, Masoud / Dawsey, Sanford M / Pharoah, Paul D / Brennan, Paul / Abnet, Christian C / Boffetta, Paolo / Kamangar, Farin / Malekzadeh, Reza. ·Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. · Surveillance and Health Services Research, American Cancer Society, Atlanta, Georgia. · Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland. · Departments of Oncology and Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. · International Agency for Research on Cancer, Lyon, France. · The Tisch Cancer Institute and Institute for Transitional Epidemiology, Mount Sinai School of Medicine, New York, New York. · School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, Maryland. · Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. malek@tums.ac.ir. ·Cancer Epidemiol Biomarkers Prev · Pubmed #29263189.

ABSTRACT:

8 Article The Role of Obesity, Type 2 Diabetes, and Metabolic Factors in Pancreatic Cancer: A Mendelian Randomization Study. 2017

Carreras-Torres, Robert / Johansson, Mattias / Gaborieau, Valerie / Haycock, Philip C / Wade, Kaitlin H / Relton, Caroline L / Martin, Richard M / Davey Smith, George / Brennan, Paul. ·Section of Genetics, International Agency for Research on Cancer (IARC), Lyon, France; MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK; National Institute for Health Research Biomedical Research Unit in Nutrition, Diet and Lifestyle at University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK. ·J Natl Cancer Inst · Pubmed #28954281.

ABSTRACT: Background: Risk factors for pancreatic cancer include a cluster of metabolic conditions such as obesity, hypertension, dyslipidemia, insulin resistance, and type 2 diabetes. Given that these risk factors are correlated, separating out causal from confounded effects is challenging. Mendelian randomization (MR), or the use of genetic instrumental variables, may facilitate the identification of the metabolic drivers of pancreatic cancer. Methods: We identified genetic instruments for obesity, body shape, dyslipidemia, insulin resistance, and type 2 diabetes in order to evaluate their causal role in pancreatic cancer etiology. These instruments were analyzed in relation to risk using a likelihood-based MR approach within a series of 7110 pancreatic cancer patients and 7264 control subjects using genome-wide data from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Potential unknown pleiotropic effects were assessed using a weighted median approach and MR-Egger sensitivity analyses. Results: Results indicated a robust causal association of increasing body mass index (BMI) with pancreatic cancer risk (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.09 to 1.65, for each standard deviation increase in BMI [4.6 kg/m2]). There was also evidence that genetically increased fasting insulin levels were causally associated with an increased risk of pancreatic cancer (OR = 1.66, 95% CI = 1.05 to 2.63, per SD [44.4 pmol/L]). Notably, no evidence of a causal relationship was observed for type 2 diabetes, nor for dyslipidemia. Sensitivity analyses did not indicate that pleiotropy was an important source of bias. Conclusions: Our results suggest a causal role of BMI and fasting insulin in pancreatic cancer etiology.

9 Article Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study. 2017

Duell, Eric J / Lujan-Barroso, Leila / Sala, Núria / Deitz McElyea, Samantha / Overvad, Kim / Tjonneland, Anne / Olsen, Anja / Weiderpass, Elisabete / Busund, Lill-Tove / Moi, Line / Muller, David / Vineis, Paolo / Aune, Dagfinn / Matullo, Giuseppe / Naccarati, Alessio / Panico, Salvatore / Tagliabue, Giovanna / Tumino, Rosario / Palli, Domenico / Kaaks, Rudolf / Katzke, Verena A / Boeing, Heiner / Bueno-de-Mesquita, H B As / Peeters, Petra H / Trichopoulou, Antonia / Lagiou, Pagona / Kotanidou, Anastasia / Travis, Ruth C / Wareham, Nick / Khaw, Kay-Tee / Ramon Quiros, Jose / Rodríguez-Barranco, Miguel / Dorronsoro, Miren / Chirlaque, María-Dolores / Ardanaz, Eva / Severi, Gianluca / Boutron-Ruault, Marie-Christine / Rebours, Vinciane / Brennan, Paul / Gunter, Marc / Scelo, Ghislaine / Cote, Greg / Sherman, Stuart / Korc, Murray. ·Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. · Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus C, Denmark. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. · Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway. · Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway. · School of Public Health, Epidemiology & Biostatistics, Imperial College London, London, United Kingdom. · Human Genetics Foundation (HuGeF), Turin, Italy. · Department of Medical Sciences, University of Turin, Turin, Italy. · Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. · Lombardy Cancer Registry Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. · Cancer Registry and Histopathology Unit, "Civic - M.P, Arezzo" Hospital, ASP, Ragusa, Italy. · Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Florence, Italy. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. · Dt. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Dt. of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. · Dt. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Dept of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · MRC-PHE Centre for Environment and Health, Dept of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. · Hellenic Health Foundation, Athens, Greece. · WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Greece. · Department of Epidemiology, Harvard School of Public Health, Boston, MA. · Department of Critical Care Medicine & Pulmonary Services, University of Athens Medical School, Evangelismos Hospital, Athens, Greece. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. · Public Health Directorate, Asturias, Spain. · Andalusian School of Public Health, Research Insititute Biosanitary Granada, University Hospital Granada/University of Granada, Granada. · CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain. · Basque Regional Health Department, San Sebatian, Spain. · Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. · Navarra Public Health Institute, Pamplona, Spain. · IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. · Gustave Roussy, Villejuif, France. · Beaujon Hospital, Pancreatology Unit, Clichy, France. · INSERM, University Paris, France. · International Agency for Research on Cancer (IARC), Lyon, France. · Medical University of South Carolina, Charleston, SC. · Departments of Medicine and Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN. · Pancreatic Cancer Signature Center, Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN. ·Int J Cancer · Pubmed #28542740.

ABSTRACT: Noninvasive biomarkers for early pancreatic ductal adenocarcinoma (PDAC) diagnosis and disease risk stratification are greatly needed. We conducted a nested case-control study within the Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate prediagnostic microRNAs (miRs) as biomarkers of subsequent PDAC risk. A panel of eight miRs (miR-10a, -10b, -21-3p, -21-5p, -30c, -106b, -155 and -212) based on previous evidence from our group was evaluated in 225 microscopically confirmed PDAC cases and 225 controls matched on center, sex, fasting status and age/date/time of blood collection. MiR levels in prediagnostic plasma samples were determined by quantitative RT-PCR. Logistic regression was used to model levels and PDAC risk, adjusting for covariates and to estimate area under the receiver operating characteristic curves (AUC). Plasma miR-10b, -21-5p, -30c and -106b levels were significantly higher in cases diagnosed within 2 years of blood collection compared to matched controls (all p-values <0.04). Based on adjusted logistic regression models, levels for six miRs (miR-10a, -10b, -21-5p, -30c, -155 and -212) overall, and for four miRs (-10a, -10b, -21-5p and -30c) at shorter follow-up time between blood collection and diagnosis (≤5 yr, ≤2 yr), were statistically significantly associated with risk. A score based on the panel showed a linear dose-response trend with risk (p-value = 0.0006). For shorter follow-up (≤5 yr), AUC for the score was 0.73, and for individual miRs ranged from 0.73 (miR-212) to 0.79 (miR-21-5p).

10 Article Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer. 2017

Capello, Michela / Bantis, Leonidas E / Scelo, Ghislaine / Zhao, Yang / Li, Peng / Dhillon, Dilsher S / Patel, Nikul J / Kundnani, Deepali L / Wang, Hong / Abbruzzese, James L / Maitra, Anirban / Tempero, Margaret A / Brand, Randall / Firpo, Matthew A / Mulvihill, Sean J / Katz, Matthew H / Brennan, Paul / Feng, Ziding / Taguchi, Ayumu / Hanash, Samir M. ·Departments of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · International Agency for Research on Cancer (IARC) Lyon, France. · Division of Medical Oncology, Duke University, Durham, NC, USA. · Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Pancreas Center, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA · Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA. · Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. ·J Natl Cancer Inst · Pubmed #28376157.

ABSTRACT: Background: CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone. Methods: Candidate biomarkers were subjected to enzyme-linked immunosorbent assay based sequential validation using independent multiple sample cohorts consisting of PDAC cases (n = 187), benign pancreatic disease (n = 93), and healthy controls (n = 169). A biomarker panel for early-stage PDAC was developed based on a logistic regression model. All statistical tests for the results presented below were one-sided. Results: Six out of the 17 biomarker candidates and CA19-9 were validated in a sample set consisting of 75 PDAC patients, 27 healthy subjects, and 19 chronic pancreatitis patients. A second independent set of 73 early-stage PDAC patients, 60 healthy subjects, and 74 benign pancreatic disease patients (combined validation set) yielded a model that consisted of TIMP1, LRG1, and CA19-9. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy subjects (test set). The model yielded areas under the curve (AUCs) of 0.949 (95% confidence interval [CI] = 0.917 to 0.981) and 0.887 (95% CI = 0.817 to 0.957) with sensitivities of 0.849 and 0.667 at 95% specificity in discriminating early-stage PDAC vs healthy subjects in the combined validation and test sets, respectively. The performance of the biomarker panel was statistically significantly improved compared with CA19-9 alone (P < .001, combined validation set; P = .008, test set). Conclusion: The addition of TIMP1 and LRG1 immunoassays to CA19-9 statistically significantly improves the detection of early-stage PDAC.

11 Article High prevalence of mutant KRAS in circulating exosome-derived DNA from early-stage pancreatic cancer patients. 2017

Allenson, K / Castillo, J / San Lucas, F A / Scelo, G / Kim, D U / Bernard, V / Davis, G / Kumar, T / Katz, M / Overman, M J / Foretova, L / Fabianova, E / Holcatova, I / Janout, V / Meric-Bernstam, F / Gascoyne, P / Wistuba, I / Varadhachary, G / Brennan, P / Hanash, S / Li, D / Maitra, A / Alvarez, H. ·Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, USA. · Genetic Epidemiology Group International Agency for Research on Cancer, Lyon, France. · Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. · Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic. · Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia. · Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic. · Department of Preventive Medicine, Palacky University of Medicine, Olomouc, Czech Republic. · Department of Epidemiology and Public Health, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic. · Department of Investigational Cancer Therapeutics and the Institute for Personalized Cancer Therapy, Houston, USA. · Section of Experimental Pathology, University of Texas M.D. Anderson Cancer Center, Houston, USA · Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA. ·Ann Oncol · Pubmed #28104621.

ABSTRACT: Background: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). Patients and methods: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival. Results: KRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls. Conclusions: Exosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

12 Article KRAS mutations in blood circulating cell-free DNA: a pancreatic cancer case-control. 2016

Le Calvez-Kelm, Florence / Foll, Matthieu / Wozniak, Magdalena B / Delhomme, Tiffany M / Durand, Geoffroy / Chopard, Priscilia / Pertesi, Maroulio / Fabianova, Eleonora / Adamcakova, Zora / Holcatova, Ivana / Foretova, Lenka / Janout, Vladimir / Vallee, Maxime P / Rinaldi, Sabina / Brennan, Paul / McKay, James D / Byrnes, Graham B / Scelo, Ghislaine. ·International Agency for Research on Cancer (IARC), Lyon, France. · Regional Authority of Public Health, Banska Bystrica, Slovakia. · Charles University of Prague, First Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague, Czech Republic. · Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Brno, Czech Republic. · Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic. · Faculty of Medicine, University of Ostrava, Czech Republic. ·Oncotarget · Pubmed #27705932.

ABSTRACT: The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series.

13 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.

14 Article Physical activity and risk of pancreatic cancer in a central European multicenter case-control study. 2014

Brenner, Darren R / Wozniak, Magdalena B / Feyt, Clément / Holcatova, Ivana / Janout, Vladimir / Foretova, Lenka / Fabianova, Eleonora / Shonova, Olga / Martinek, Arnost / Ryska, Miroslav / Adamcakova, Zora / Flaska, Erik / Moskal, Aurelie / Brennan, Paul / Scelo, Ghislaine. ·Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69372, Lyon Cedex 08, France. ·Cancer Causes Control · Pubmed #24695987.

ABSTRACT: PURPOSE: Findings from epidemiological studies examining physical activity in relation to pancreatic cancer risk have suggested decreased risks for physical activity; however, the results are inconsistent. METHODS: The association between occupational and leisure-time physical activity and risk of pancreatic cancer was examined among 826 pancreatic cancer cases and 930 age-, sex- and center-matched controls from a large multicenter central European study in Czech Republic and Slovakia recruited between 2004 and 2012. Data on physical activity including type and dose (frequency, intensity, and duration) were examined using multivariable-adjusted logistic regression models. RESULTS: Occupational physical activity was not significantly associated with risk of pancreatic cancer [odds ratio (OR) 0.90, 95 % confidence interval (CI) 0.71-1.15]. A 35 % decrease in risk of pancreatic cancer was observed for regular leisure-time physical activity (OR 0.65, 95 % CI 0.52-0.87). The risk estimates were significant for low and moderate intensity of activity with the strongest protective effect among individuals who exercised during more than 40 weeks per year. The results for cumulated leisure-time physical activity assessed 1 year prior to diagnosis achieved the same level of risk reduction. In addition, stronger risk estimates for leisure-time physical activity were observed among women (men: OR 0.74, 95 % CI 0.54-1.01; women: OR 0.53, 95 % CI 0.37-0.75). The findings for female participants were stronger for intensity and frequency of leisure-time physical activity, in particular for light and moderate activity (OR 0.43, 95 % CI 0.25-0.75; and OR 0.57, 95 % CI 0.37-0.88, respectively). CONCLUSION: These results provide evidence for a decreased risk of pancreatic cancer associated with regular leisure-time physical activity.

15 Article Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case-control study. 2011

Urayama, Kevin Y / Holcatova, Ivana / Janout, Vladimir / Foretova, Lenka / Fabianova, Eleonora / Adamcakova, Zora / Ryska, Miroslav / Martinek, Arnost / Shonova, Olga / Brennan, Paul / Scélo, Ghislaine. ·International Agency for Research on Cancer, Lyon, France. ·Int J Cancer · Pubmed #21520034.

ABSTRACT: The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency-matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at 2 years before the interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR = 1.86, 95% CI: 1.32, 2.62) and body size (OR = 1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood.