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Pancreatic Neoplasms: HELP
Articles by Rudolph Kaaks
Based on 35 articles published since 2009
(Why 35 articles?)
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Between 2009 and 2019, R. Kaaks wrote the following 35 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Diabetes mellitus type 2 - an independent risk factor for cancer? 2010

Grote, V A / Becker, S / Kaaks, R. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Exp Clin Endocrinol Diabetes · Pubmed #20127570.

ABSTRACT: Epidemiological findings have shown up to two-fold increases in the risks of cancers of the colorectum, breast, endometrium, kidney (renal cell tumours), liver and pancreas among diabetes patients. In the present review, we address the question whether, on the basis of these epidemiological observations, type 2 diabetes should be considered a specific and independent risk factor for these various forms of cancer, due to its particular metabolic characteristics of glucose intolerance and hyperinsulinemia. On the basis of further epidemiological evidence among non-diabetic individuals, as well as recent studies examining the effects of different types of diabetes treatment on cancer risks, we conclude that chronic elevations in fasting and non-fasting blood levels of glucose and/or insulin are plausible independent risk factors for cancer, but that much of the increase in cancer risks associated with these two metabolic factors may occur within the normoglycaemic and insulinemic (non-diabetic) ranges. Furthermore, for some tumour types (e. g. cancer of the endometrium) the associations of risk with type 2 diabetes may to a large extent be due to, and at least partially confounded by, other obesity-related alterations in (e. g. sex steroid) metabolism that in part are independent of glucose and/or insulin metabolism. Specifically for pancreatic cancer, a major question, addressed in detail by other reviews, is whether associations of risk with plasma glucose, insulin or overt type 2 diabetes could be either a cause, or possibly also a consequence of tumour development (or both).

2 Review Obesity related hyperinsulinaemia and hyperglycaemia and cancer development. 2009

Becker, Susen / Dossus, Laure / Kaaks, Rudolf. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. ·Arch Physiol Biochem · Pubmed #19485704.

ABSTRACT: Excess body weight in combination with physical inactivity is a major determinant for the development of insulin resistance with associated hyperglycaemia and hyperinsulinaemia and further leads to tumour development. Several prospective epidemiological studies have shown a direct association between excess weight and common malignancies, such as colon, breast (post-menopausal), endometrial, gallbladder, pancreatic, kidney and oesophageal cancers, but also less frequent malignancies, such as leukaemia, multiple myeloma and non-Hodgkin lymphoma. Insulin resistance and hyperinsulinaemia are certainly key biological mechanisms underlying the relationship between adiposity and tumour development. The anti-diabetic drug, metformin, in addition to reduction of insulin resistance has also shown anti-tumour properties, and is increasingly being considered as a drug to prevent and treat obesity-related cancers. Several biological pathways have been involved in the association between excess body weight, insulin resistance and cancer, such as chronic low-grade inflammation, glucose toxicity, AGE product metabolism and the adenosine monophosphate kinase pathway.

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 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.

5 Article Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort. 2018

Matejcic, M / Lesueur, F / Biessy, C / Renault, A L / Mebirouk, N / Yammine, S / Keski-Rahkonen, P / Li, K / Hémon, B / Weiderpass, E / Rebours, V / Boutron-Ruault, M C / Carbonnel, F / Kaaks, R / Katzke, V / Kuhn, T / Boeing, H / Trichopoulou, A / Palli, D / Agnoli, C / Panico, S / Tumino, R / Sacerdote, C / Quirós, J R / Duell, E J / Porta, M / Sánchez, M J / Chirlaque, M D / Barricarte, A / Amiano, P / Ye, W / Peeters, P H / Khaw, K T / Perez-Cornago, A / Key, T J / Bueno-de-Mesquita, H B / Riboli, E / Vineis, P / Romieu, I / Gunter, M J / Chajès, V. ·International Agency for Research on Cancer, Lyon, France. · Genetic Epidemiology of Cancer team, Inserm, U900, Paris, France. · Institut Curie, Paris, France. · PSL University, Paris, France. · Mines ParisTech, Fontainebleau, France. · Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · 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. · Public Health Division of Gipuzkoa, BioDonostia Research institute, San Sebastian, Spain. · Department of Gastroenterology and Pancreatology, Beaujon Hospital, University Paris 7, Clichy, France. · INSERM, Centre for Research in Epidemiology and Population Health, U1018, Health across Generations Team, Institut Gustave Roussy, Villejuif, France. · Université Paris Sud, UMRS, Villejuif, France. · Department of Gastroenterology, Bicêtre University Hospital, Assistance Publique des Hôpitaux de Paris, Le Kremlin Bicêtre, France. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. · Hellenic Health Foundation, Athens, Greece. · WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. · Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Clinical Medicine and Surgery Department, Università degli Studi di Napoli Federico II, Naples, Italy. · Cancer Registry and Histopathology Department, ASP, "Civic - M.P. Arezzo" Hospital, Ragusa, Italy. · Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital, University of Turin and Centre for Cancer Prevention (CPO), Turin, Italy. · EPIC Asturias, Public Health Directorate, Asturias, Spain. · Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Hospital del Mar Research Institute - IMIM, CIBER Epidemiología y Salud Pública (CIBERESP) and Universitat Autònoma de Barcelona, Barcelona, Spain. · Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain. · Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. · Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. · Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. · Navarra Public Health Institute, Pamplona, Spain. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · The Medical Biobank at Umeå University, Umeå, Sweden. · 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, United Kingdom. · University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · MRC-PHE Center for Environment and Health, School of Public Health, Imperial College, London, United Kingdom. ·Int J Cancer · Pubmed #30110135.

ABSTRACT: There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (OR

6 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.

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 Lack of Association for Reported Endocrine Pancreatic Cancer Risk Loci in the PANDoRA Consortium. 2017

Campa, Daniele / Obazee, Ofure / Pastore, Manuela / Panzuto, Francesco / Liço, Valbona / Greenhalf, William / Katzke, Verena / Tavano, Francesca / Costello, Eithne / Corbo, Vincenzo / Talar-Wojnarowska, Renata / Strobel, Oliver / Zambon, Carlo Federico / Neoptolemos, John P / Zerboni, Giulia / Kaaks, Rudolf / Key, Timothy J / Lombardo, Carlo / Jamroziak, Krzysztof / Gioffreda, Domenica / Hackert, Thilo / Khaw, Kay-Tee / Landi, Stefano / Milanetto, Anna Caterina / Landoni, Luca / Lawlor, Rita T / Bambi, Franco / Pirozzi, Felice / Basso, Daniela / Pasquali, Claudio / Capurso, Gabriele / 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. · Pancreatic and Digestive Endocrine Surgery, Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Padua, Italy. · Institute of Translational Medicine, Cancer Research UK Liverpool Cancer Trials Unit, Liverpool, United Kingdom. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Gastroenterology and Research Laboratory, Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Department of Medicine - DIMED, University of Padova, Padua, Italy. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, 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. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom. · The Pancreas Institute, Department of Surgery, University and Hospital Trust of Verona, Verona, Italy. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. f.canzian@dkfz.de. ·Cancer Epidemiol Biomarkers Prev · Pubmed #28765340.

ABSTRACT:

10 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).

11 Article Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study. 2017

Huang, Jiaqi / Zagai, Ulrika / Hallmans, Göran / Nyrén, Olof / Engstrand, Lars / Stolzenberg-Solomon, Rachael / Duell, Eric J / Overvad, Kim / Katzke, Verena A / Kaaks, Rudolf / Jenab, Mazda / Park, Jin Young / Murillo, Raul / Trichopoulou, Antonia / Lagiou, Pagona / Bamia, Christina / Bradbury, Kathryn E / Riboli, Elio / Aune, Dagfinn / Tsilidis, Konstantinos K / Capellá, Gabriel / Agudo, Antonio / Krogh, Vittorio / Palli, Domenico / Panico, Salvatore / Weiderpass, Elisabete / Tjønneland, Anne / Olsen, Anja / Martínez, Begoña / Redondo-Sanchez, Daniel / Chirlaque, Maria-Dolores / Hm Peeters, Petra / Regnér, Sara / Lindkvist, Björn / Naccarati, Alessio / Ardanaz, Eva / Larrañaga, Nerea / Boutron-Ruault, Marie-Christine / Rebours, Vinciane / Barré, Amélie / Bueno-de-Mesquita, H B As / Ye, Weimin. ·Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden. · Department of Public Health and Clinical Nutrition, Umeå University, Umeå, Sweden. · Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. · Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD. · Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Prevention and Implementation Group, Section of Early Detection and Prevention, Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. · Hellenic Health Foundation, Athens, Greece. · WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. · Translational Research Laboratory, IDIBELL-Catalan Institute of Oncology, Barcelona, Spain. · Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. · Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. · Dipartimento di medicina clinica e chirurgia Federico II, Naples, Italy. · Department of Community Medicine, 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. · Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Andalusian School of Public Health, Instituto De Investigación Biosanitaria Ibs, Granada, Spain. · CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. · Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. · Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Surgery, Institution of Clinical Sciences Malmö, Lund University, Malmö, Sweden. · Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. · Molecular and Genetic Epidemiology Unit, Human Genetics Foundation, Turin, Italy. · Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Spain. · Hormones and Women's Health Team, INSERM, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Villejuif, F-94805, France. · Université Paris Sud, UMRS 1018, Villejuif, F-94805, France. · Institut Gustave Roussy, Villejuif, F-94805, France. · Department of Gastroenterology and Pancreatology, Beaujon Hospital, University Paris 7, Clichy, France. · Université Paris Sud and Gastroenterology Unit, Hôpitaux Universitaires Paris Sud, CHU de Bicêtre, AP-HP, Le Kremlin Bicêtre, France. · 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 & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · The Medical Biobank at Umeå University, Umeå, Sweden. ·Int J Cancer · Pubmed #28032715.

ABSTRACT: The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.

12 Article Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors. 2016

Campa, Daniele / Capurso, Gabriele / Pastore, Manuela / Talar-Wojnarowska, Renata / Milanetto, Anna Caterina / Landoni, Luca / Maiello, Evaristo / Lawlor, Rita T / Malecka-Panas, Ewa / Funel, Niccola / Gazouli, Maria / De Bonis, Antonio / Klüter, Harald / Rinzivillo, Maria / Delle Fave, Gianfranco / Hackert, Thilo / Landi, Stefano / Bugert, Peter / Bambi, Franco / Archibugi, Livia / Scarpa, Aldo / Katzke, Verena / Dervenis, Christos / Liço, Valbona / Furlanello, Sara / Strobel, Oliver / Tavano, Francesca / Basso, Daniela / Kaaks, Rudolf / Pasquali, Claudio / Gentiluomo, Manuel / Rizzato, Cosmeri / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Dept of Digestive Tract Diseases, Medical University of Lodz, Poland. · Department of Surgery, Oncology and Gastroenterology (DISCOG), Pancreatic and Digestive Endocrine Surgery, University of Padova, Padova, Italy. · Department of Surgery, University and Hospital Trust of Verona, Verona, Italy. · Department of Oncology, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School National and Kapodistrian University of Athens, Greece. · Department of Surgery, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Mannheim Institute of Transfusion Medicine and Immunology, Heidelberg University, Medical Faculty Mannheim, German Red Cross Blood Service Baden-Württemberg - Hessen, Mannheim, Germany. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Blood Transfusion Service, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Surgery, Konstantopouleion General Hospital Nea Ionia, Greece. · Department of Medicine (DIMED), Laboratory Medicine, University of Padova, Padova, Italy. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. ·Sci Rep · Pubmed #28008994.

ABSTRACT: Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (OR

13 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.

14 Article Functional single nucleotide polymorphisms within the cyclin-dependent kinase inhibitor 2A/2B region affect pancreatic cancer risk. 2016

Campa, Daniele / Pastore, Manuela / Gentiluomo, Manuel / Talar-Wojnarowska, Renata / Kupcinskas, Juozas / Malecka-Panas, Ewa / Neoptolemos, John P / Niesen, Willem / Vodicka, Pavel / Delle Fave, Gianfranco / Bueno-de-Mesquita, H Bas / Gazouli, Maria / Pacetti, Paola / Di Leo, Milena / Ito, Hidemi / Klüter, Harald / Soucek, Pavel / Corbo, Vincenzo / Yamao, Kenji / Hosono, Satoyo / Kaaks, Rudolf / Vashist, Yogesh / Gioffreda, Domenica / Strobel, Oliver / Shimizu, Yasuhiro / Dijk, Frederike / Andriulli, Angelo / Ivanauskas, Audrius / Bugert, Peter / Tavano, Francesca / Vodickova, Ludmila / Zambon, Carlo Federico / Lovecek, Martin / Landi, Stefano / Key, Timothy J / Boggi, Ugo / Pezzilli, Raffaele / Jamroziak, Krzysztof / Mohelnikova-Duchonova, Beatrice / Mambrini, Andrea / Bambi, Franco / Busch, Olivier / Pazienza, Valerio / Valente, Roberto / Theodoropoulos, George E / Hackert, Thilo / Capurso, Gabriele / Cavestro, Giulia Martina / Pasquali, Claudio / Basso, Daniela / Sperti, Cosimo / Matsuo, Keitaro / Büchler, Markus / Khaw, Kay-Tee / Izbicki, Jakob / Costello, Eithne / Katzke, Verena / Michalski, Christoph / Stepien, Anna / Rizzato, Cosmeri / Canzian, Federico. ·Department of Biology, University of Pisa, Pisa, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania. · Institute for Health Research Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool, United Kingdom. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Institute of Experimental Medicine, Czech Academy of Science, Prague, Czech Republic. · Institute of Biology and Medical Genetics, 1st Medical Faculty, Charles University, Prague, Czech Republic. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. · Department 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. · Department of Basic Medical Sciences, Laboratory of Biology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Oncological Department Massa Carrara Azienda USL Toscana Nord Ovest, Carrara, Italy. · Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Division Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. · Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg - Hessen gGmbH, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. · Laboratory of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · ARC-Net Research Centre, and Department of Diagnostics and Public Health University and Hospital Trust of Verona, Verona, Italy. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands. · Biomedical Center, Faculty of Medicine in Pilsen, Charles University in Prague, Prague, Czech Republic. · Department of Medicine - DIMED, University of Padova, Padova, Italy. · Department of Surgery I, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Epidemiology Unit Nuffield Department of Population Health University of Oxford, Oxford, UK. · Division of General and Transplant Surgery, Pisa University Hospital, Pisa, Italy. · Pancreas Unit, Department of Digestive System, Dant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Hematology, Institute of Hematology and Transfusion Medicine, Warsaw, Poland. · Department of Oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic. · Blood Transfusion Service, Azienda Ospedaliero Universitaria Meyer, Florence, Italy. · Department of Surgery, Academic Medical Centre, Amsterdam, The Netherlands. · Colorectal Unit, First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece. · Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy. · Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan. · Clinical Gerontology Unit, Addenbrooke’s Hospital, School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Laboratory of Clinical, Transplant Immunology and Genetics, Copernicus Memorial Hospital, Lodz, Poland. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. ·Oncotarget · Pubmed #27486979.

ABSTRACT: The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.

15 Article Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms. 2015

Cifarelli, Vincenza / Lashinger, Laura M / Devlin, Kaylyn L / Dunlap, Sarah M / Huang, Jennifer / Kaaks, Rudolf / Pollak, Michael N / Hursting, Stephen D. ·Department of Medicine, Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO. · Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX. · Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX. · Division of Epidemiology, German Cancer Research Center, Heidelberg, Germany. · Departments of Medicine and Oncology, McGill University, Montreal, Canada. · Department of Nutritional Sciences, The University of Texas at Austin, Austin, TX Department of Nutrition, University of North Carolina, Chapel Hill, NC Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC hursting@email.unc.edu. ·Diabetes · Pubmed #25576058.

ABSTRACT: Metformin treatment is associated with a decreased risk and better prognosis of pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of metformin's PC growth inhibition in the context of a prediabetic state is unknown. We used a Panc02 pancreatic tumor cell transplant model in diet-induced obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose regulation, mTOR pathway signaling, and candidate microRNA (miR) expression. In DIO/prediabetic mice, metformin and rapamycin significantly reduced pancreatic tumor growth and mTOR-related signaling. The rapamycin effects centered on decreased mTOR-regulated growth and survival signaling, including increased expression of let-7b and cell cycle-regulating miRs. Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail. Metformin also reduced the number and size of Panc02 tumor spheres in vitro and inhibited the expression of Notch in spheroids. Our results suggest that metformin and rapamycin can both inhibit pancreatic tumor growth in obese, prediabetic mice through shared and distinct mechanisms. Metformin and direct mTOR inhibitors, alone or possibly in combination, represent promising intervention strategies for breaking the diabetes-PC link.

16 Article Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk. 2015

Jeurnink, Suzanne M / Ros, Martine M / Leenders, Max / van Duijnhoven, Franzel J B / Siersema, Peter D / Jansen, Eugene H J M / van Gils, Carla H / Bakker, Marije F / Overvad, Kim / Roswall, Nina / Tjønneland, Anne / Boutron-Ruault, Marie-Christine / Racine, Antoine / Cadeau, Claire / Grote, Verena / Kaaks, Rudolf / Aleksandrova, Krasimira / Boeing, Heiner / Trichopoulou, Antonia / Benetou, Vasiliki / Valanou, Elisavet / Palli, Domenico / Krogh, Vittorio / Vineis, Paolo / Tumino, Rosario / Mattiello, Amalia / Weiderpass, Elisabete / Skeie, Guri / Castaño, José María Huerta / Duell, Eric J / Barricarte, Aurelio / Molina-Montes, Esther / Argüelles, Marcial / Dorronsoro, Mire / Johansen, Dorthe / Lindkvist, Björn / Sund, Malin / Crowe, Francesca L / Khaw, Kay-Tee / Jenab, Mazda / Fedirko, Veronika / Riboli, E / Bueno-de-Mesquita, H B. ·Department of Gastroenterology and Hepatology, University Medical Center Utrecht, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. ·Int J Cancer · Pubmed #25175624.

ABSTRACT: Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and β-carotene, lycopene, β-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma β-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and β-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of β-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted.

17 Article Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study. 2014

Campa, Daniele / Mergarten, Björn / De Vivo, Immaculata / Boutron-Ruault, Marie-Christine / Racine, Antoine / Severi, Gianluca / Nieters, Alexandra / Katzke, Verena A / Trichopoulou, Antonia / Yiannakouris, Nikos / Trichopoulos, Dimitrios / Boeing, Heiner / Quirós, J Ramón / Duell, Eric J / Molina-Montes, Esther / Huerta, José María / Ardanaz, Eva / Dorronsoro, Miren / Khaw, Kay-Tee / Wareham, Nicholas / Travis, Ruth C / Palli, Domenico / Pala, Valeria / Tumino, Rosario / Naccarati, Alessio / Panico, Salvatore / Vineis, Paolo / Riboli, Elio / Siddiq, Afshan / Bueno-de-Mesquita, H B / Peeters, Petra H / Nilsson, Peter M / Sund, Malin / Ye, Weimin / Lund, Eiliv / Jareid, Mie / Weiderpass, Elisabete / Duarte-Salles, Talita / Kong, So Yeon / Stepien, Magdalena / Canzian, Federico / Kaaks, Rudolf. ·Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts. · Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones, and Women's Health team, Villejuif, France. Univ Paris Sud, UMRS 1018, Villejuif, France. IGR, Villejuif, France. · Human Genetics Foundation (HuGeF), Torino, Italy. · Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany. · Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. · Hellenic Health Foundation, Athens, Greece. Harokopio University of Athens, Greece. · Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. · Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. · Public Health Directorate, Asturias, Spain. · Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain. · Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. · CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. · CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. Navarre Public Health Institute, Pamplona, Spain. · Public Health Direction and Biodonostia-Ciberesp Basque Regional Health Department, San Sebastian, Spain. · University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom. · Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom. · Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, ISPO, Florence, Italy. · Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Ragusa, Italy. · Dipartimento Di Medicina Clinica e Chirurgia Federico II University, Naples, Italy. · Division of Epidemiology, Public Health and Primary Care, Imperial College, London, United Kingdom. · Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, United Kingdom. · National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. The School of Public Health, Imperial College London, London, United Kingdom. · Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands. · Lund University, Department of Clinical Sciences, Skåne University Hospital, Malmö Sweden. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. The Medical Biobank at Umeå University, Umeå, Sweden. · Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. · Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. · International Agency for Research on Cancer (IARC-WHO), Lyon, France. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. r.kaaks@dkfz.de. ·Cancer Epidemiol Biomarkers Prev · Pubmed #25103821.

ABSTRACT: BACKGROUND: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. METHODS: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). RESULTS: We observed that the mean LTL was higher in cases (0.59 ± 0.20) than in controls (0.57 ± 0.17), although this difference was not statistically significant (P = 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01-1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P = 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL. CONCLUSION: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. IMPACT: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk.

18 Article Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. 2014

Wolpin, Brian M / Rizzato, Cosmeri / Kraft, Peter / Kooperberg, Charles / Petersen, Gloria M / Wang, Zhaoming / Arslan, Alan A / Beane-Freeman, Laura / Bracci, Paige M / Buring, Julie / Canzian, Federico / Duell, Eric J / Gallinger, Steven / Giles, Graham G / Goodman, Gary E / Goodman, Phyllis J / Jacobs, Eric J / Kamineni, Aruna / Klein, Alison P / Kolonel, Laurence N / Kulke, Matthew H / Li, Donghui / Malats, Núria / Olson, Sara H / Risch, Harvey A / Sesso, Howard D / Visvanathan, Kala / White, Emily / Zheng, Wei / Abnet, Christian C / Albanes, Demetrius / Andreotti, Gabriella / Austin, Melissa A / Barfield, Richard / Basso, Daniela / Berndt, Sonja I / Boutron-Ruault, Marie-Christine / Brotzman, Michelle / Büchler, Markus W / Bueno-de-Mesquita, H Bas / Bugert, Peter / Burdette, Laurie / Campa, Daniele / Caporaso, Neil E / Capurso, Gabriele / Chung, Charles / Cotterchio, Michelle / Costello, Eithne / Elena, Joanne / Funel, Niccola / Gaziano, J Michael / Giese, Nathalia A / Giovannucci, Edward L / Goggins, Michael / Gorman, Megan J / Gross, Myron / Haiman, Christopher A / Hassan, Manal / Helzlsouer, Kathy J / Henderson, Brian E / Holly, Elizabeth A / Hu, Nan / Hunter, David J / Innocenti, Federico / Jenab, Mazda / Kaaks, Rudolf / Key, Timothy J / Khaw, Kay-Tee / Klein, Eric A / Kogevinas, Manolis / Krogh, Vittorio / Kupcinskas, Juozas / Kurtz, Robert C / LaCroix, Andrea / Landi, Maria T / Landi, Stefano / Le Marchand, Loic / Mambrini, Andrea / Mannisto, Satu / Milne, Roger L / Nakamura, Yusuke / Oberg, Ann L / Owzar, Kouros / Patel, Alpa V / Peeters, Petra H M / Peters, Ulrike / Pezzilli, Raffaele / Piepoli, Ada / Porta, Miquel / Real, Francisco X / Riboli, Elio / Rothman, Nathaniel / Scarpa, Aldo / Shu, Xiao-Ou / Silverman, Debra T / Soucek, Pavel / Sund, Malin / Talar-Wojnarowska, Renata / Taylor, Philip R / Theodoropoulos, George E / Thornquist, Mark / Tjønneland, Anne / Tobias, Geoffrey S / Trichopoulos, Dimitrios / Vodicka, Pavel / Wactawski-Wende, Jean / Wentzensen, Nicolas / Wu, Chen / Yu, Herbert / Yu, Kai / Zeleniuch-Jacquotte, Anne / Hoover, Robert / Hartge, Patricia / Fuchs, Charles / Chanock, Stephen J / Stolzenberg-Solomon, Rachael S / Amundadottir, Laufey T. ·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. [3]. · 1] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2]. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. [3]. · 1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2]. · 1] Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. [2]. · 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2] 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. · 1] Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA. [2] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [3] New York University Cancer Institute, New York, New York, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. · Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA. · 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada. · 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. [3] 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. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA. · Group Health Research Institute, Seattle, Washington, USA. · 1] Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland, USA. · The Cancer Research Center of Hawaii (retired), Honolulu, Hawaii, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, 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 Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. · 1] Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington, USA. · 1] Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. [2] Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department of Epidemiology, University of Washington, Seattle, Washington, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy. · 1] INSERM, Centre for Research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women's Health Team, Villejuif, France. [2] University Paris Sud, UMRS 1018, Villejuif, France. [3] Institut Gustave Roussy (IGR), Villejuif, France. · Westat, Rockville, Maryland, USA. · Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany. · 1] National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. [2] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands. [3] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. · Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany. · Division of Cancer Epidemiology, DKFZ, Heidelberg, Germany. · Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy. · 1] Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada. [2] 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, UK. · 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. · 1] Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, USA. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · 1] Department of Pathology, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [2] Department of Medicine, Sidney Kimmel Cancer Center and Johns Hopkins University, Baltimore, Maryland, USA. [3] 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. · Prevention and Research Center, Mercy Medical Center, Baltimore, Maryland, USA. · Cancer Prevention, University of Southern California, Los Angeles, California, USA. · 1] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Harvard School of Public Health, Boston, Massachusetts, USA. [3] Harvard Medical School, Boston, Massachusetts, USA. · The University of North Carolina Eshelman School of Pharmacy, Center for Pharmacogenomics and Individualized Therapy, Lineberger Comprehensive Cancer Center, School of Medicine, Chapel Hill, North Carolina, USA. · International Agency for Research on Cancer, Lyon, France. · Cancer Epidemiology Unit, University of Oxford, Oxford, UK. · School of Clinical Medicine, University of Cambridge, Cambridge, UK. · Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio, USA. · 1] Centre de Recerca en Epidemiologia Ambiental (CREAL), CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. [2] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [3] Department of Nutrition, 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. · Department of Biology, University of Pisa, Pisa, Italy. · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA. · Oncology Department, ASL1 Massa Carrara, Massa Carrara, Italy. · Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland. · 1] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, Australia. [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia. · Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. · Alliance Statistics and Data Center, Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Alliance Statistics and Data Center, Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA. · 1] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 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ABSTRACT: We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

19 Article Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33. 2014

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Haven, CT, USA. · Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea. · Karmanos Cancer Institute and Department of Oncology and. · Karmanos Cancer Institute and Department of Family Medicine and Public Health Sciences, Wayne State University School of Medicine, Detroit, MI, USA. · Maine Cancer Registry, Augusta, ME, USA. · Centre for Research in Occupational Health, Universitat Pompeu Fabra, Barcelona, Spain, CIBER of Epidemiology and Public Health (CIBERESP). · Department of Biostatistics, MD Anderson Cancer Center, Houston, TX, USA. · Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK. · Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Department of Surgery, Division of Cardiothoracic Surgery, Queen Mary Hospital, Hong Kong, China. · Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany. · Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia. · University of Minnesota, Minneapolis, MN, USA. · Dan L. Duncan Center, Baylor College of Medicine, Houston, TX, USA. · Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. · Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, Tainan, Taiwan. · Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Umeå, Sweden. · Department of Thoracic and Cardiovascular Surgery, Seoul St Mary's Hospital, Seoul, South Korea. · Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK, Division of Breast Cancer Research, Institute of Cancer Research, London, UK. · Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain. · Sir Peter MacCallum Department of Oncology, University of Melbourne, St Andrew's Place, East Melbourne, VIC, Australia. · Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. · Department of Pulmonary Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan. · Cancer Registry Associazione Iblea Ricerca Epidemiologica, Onlus and Asp Ragusa, Ragusa Italy. · Kaiser Permanente Northern California, Oakland, CA, USA. · Division of Environmental Epidemiology, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. · Imperial College, London, UK, Human Genetics Foundation (HuGeF), Torino Italy. · National Research Centre for the Working Environment, Copenhagen, Denmark, National Food Institute, Technical University of Denmark, Soborg, Denmark. · Division of Cancer Epidemiology and Genetics, Cancer Genomics Research Laboratory, National Cancer Institute, Division of Cancer Epidemiology and Genetics, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA, Department of Biochemistry and Centre for Genomic Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. · Division of Cancer Etiology, Department of Population Sciences, City of Hope and the Beckman Research Institute, Duarte, CA, USA. · 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, Oslo, Norway, Department of Medical Epidemiology and Biostatistics and Samfundet Folkhälsan, Helsinki, Finland. · University of California San Francisco, San Francisco, CA, USA. · Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · Department of Pathology and. · Guangdong Lung Cancer Institute, Medical Research Center and Cancer Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. · School of Public Health, Li Ka Shing (LKS) Faculty of Medicine, The University of Hong Kong, Hong Kong, China. · Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital and. · University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA and. · Department of Population Health, New York University School of Medicine, New York, NY, USA, New York University Cancer Institute, New York, NY, USA. · Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. · Division of Cancer Epidemiology and Genetics, amundadottirl@mail.nih.gov. ·Hum Mol Genet · Pubmed #25027329.

ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

20 Article Axonal guidance signaling pathway interacting with smoking in modifying the risk of pancreatic cancer: a gene- and pathway-based interaction analysis of GWAS data. 2014

Tang, Hongwei / Wei, Peng / Duell, Eric J / Risch, Harvey A / Olson, Sara H / Bueno-de-Mesquita, H Bas / Gallinger, Steven / Holly, Elizabeth A / Petersen, Gloria / Bracci, Paige M / McWilliams, Robert R / Jenab, Mazda / Riboli, Elio / Tjønneland, Anne / Boutron-Ruault, Marie Christine / Kaaks, Rudolph / Trichopoulos, Dimitrios / Panico, Salvatore / Sund, Malin / Peeters, Petra H M / Khaw, Kay-Tee / Amos, Christopher I / Li, Donghui. ·Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ·Carcinogenesis · Pubmed #24419231.

ABSTRACT: Cigarette smoking is the best established modifiable risk factor for pancreatic cancer. Genetic factors that underlie smoking-related pancreatic cancer have previously not been examined at the genome-wide level. Taking advantage of the existing Genome-wide association study (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study in 2028 cases and 2109 controls to examine gene-smoking interactions at pathway/gene/single nucleotide polymorphism (SNP) level. Using the likelihood ratio test nested in logistic regression models and ingenuity pathway analysis (IPA), we examined 172 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, 3 manually curated gene sets, 3 nicotine dependency gene ontology pathways, 17 912 genes and 468 114 SNPs. None of the individual pathway/gene/SNP showed significant interaction with smoking after adjusting for multiple comparisons. Six KEGG pathways showed nominal interactions (P < 0.05) with smoking, and the top two are the pancreatic secretion and salivary secretion pathways (major contributing genes: RAB8A, PLCB and CTRB1). Nine genes, i.e. ZBED2, EXO1, PSG2, SLC36A1, CLSTN1, MTHFSD, FAT2, IL10RB and ATXN2 had P interaction < 0.0005. Five intergenic region SNPs and two SNPs of the EVC and KCNIP4 genes had P interaction < 0.00003. In IPA analysis of genes with nominal interactions with smoking, axonal guidance signaling $$\left(P=2.12\times 1{0}^{-7}\right)$$ and α-adrenergic signaling $$\left(P=2.52\times 1{0}^{-5}\right)$$ genes were significantly overrepresented canonical pathways. Genes contributing to the axon guidance signaling pathway included the SLIT/ROBO signaling genes that were frequently altered in pancreatic cancer. These observations need to be confirmed in additional data set. Once confirmed, it will open a new avenue to unveiling the etiology of smoking-associated pancreatic cancer.

21 Article Genes-environment interactions in obesity- and diabetes-associated pancreatic cancer: a GWAS data analysis. 2014

Tang, Hongwei / Wei, Peng / Duell, Eric J / Risch, Harvey A / Olson, Sara H / Bueno-de-Mesquita, H Bas / Gallinger, Steven / Holly, Elizabeth A / Petersen, Gloria M / Bracci, Paige M / McWilliams, Robert R / Jenab, Mazda / Riboli, Elio / Tjønneland, Anne / Boutron-Ruault, Marie Christine / Kaaks, Rudolf / Trichopoulos, Dimitrios / Panico, Salvatore / Sund, Malin / Peeters, Petra H M / Khaw, Kay-Tee / Amos, Christopher I / Li, Donghui. ·Authors' Affiliations: Departments of Gastrointestinal Medical Oncology and Epidemiology, The University of Texas MD Anderson Cancer Center; Division of Biostatistics and Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, Texas; Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain; Yale University School of Public Health, New Haven, Connecticut; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; National Institute for Public Health and the Environment (RIVM), Bilthoven and Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; Samuel Lunenfeld Research Institute, Toronto General Hospital, University of Toronto, Toronto, Canada; Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, California; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; International Agency for Research on Cancer, Lyon; Institut national de la santé et de la recherche medicale (INSERM), Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health team; Univ. Paris Sud, UMRS 1018; IGR, F-94805, Villejuif, France; Division of Epidemiology, Public Health, and Primary Care, Imperial College London, London; School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts; Bureau of Epidemiologic Research, Academy of Athens; Hellenic Health Foundation, Athens, Greece; Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy; and Department ·Cancer Epidemiol Biomarkers Prev · Pubmed #24136929.

ABSTRACT: BACKGROUND: Obesity and diabetes are potentially alterable risk factors for pancreatic cancer. Genetic factors that modify the associations of obesity and diabetes with pancreatic cancer have previously not been examined at the genome-wide level. METHODS: Using genome-wide association studies (GWAS) genotype and risk factor data from the Pancreatic Cancer Case Control Consortium, we conducted a discovery study of 2,028 cases and 2,109 controls to examine gene-obesity and gene-diabetes interactions in relation to pancreatic cancer risk by using the likelihood-ratio test nested in logistic regression models and Ingenuity Pathway Analysis (IPA). RESULTS: After adjusting for multiple comparisons, a significant interaction of the chemokine signaling pathway with obesity (P = 3.29 × 10(-6)) and a near significant interaction of calcium signaling pathway with diabetes (P = 1.57 × 10(-4)) in modifying the risk of pancreatic cancer were observed. These findings were supported by results from IPA analysis of the top genes with nominal interactions. The major contributing genes to the two top pathways include GNGT2, RELA, TIAM1, and GNAS. None of the individual genes or single-nucleotide polymorphism (SNP) except one SNP remained significant after adjusting for multiple testing. Notably, SNP rs10818684 of the PTGS1 gene showed an interaction with diabetes (P = 7.91 × 10(-7)) at a false discovery rate of 6%. CONCLUSIONS: Genetic variations in inflammatory response and insulin resistance may affect the risk of obesity- and diabetes-related pancreatic cancer. These observations should be replicated in additional large datasets. IMPACT: A gene-environment interaction analysis may provide new insights into the genetic susceptibility and molecular mechanisms of obesity- and diabetes-related pancreatic cancer.

22 Article Dietary intake of acrylamide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 2013

Obón-Santacana, M / Slimani, N / Lujan-Barroso, L / Travier, N / Hallmans, G / Freisling, H / Ferrari, P / Boutron-Ruault, M C / Racine, A / Clavel, F / Saieva, C / Pala, V / Tumino, R / Mattiello, A / Vineis, P / Argüelles, M / Ardanaz, E / Amiano, P / Navarro, C / Sánchez, M J / Molina Montes, E / Key, T / Khaw, K-T / Wareham, N / Peeters, P H / Trichopoulou, A / Bamia, C / Trichopoulos, D / Boeing, H / Kaaks, R / Katzke, V / Ye, W / Sund, M / Ericson, U / Wirfält, E / Overvad, K / Tjønneland, A / Olsen, A / Skeie, G / Åsli, L A / Weiderpass, E / Riboli, E / Bueno-de-Mesquita, H B / Duell, E J. ·Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. ·Ann Oncol · Pubmed #23857962.

ABSTRACT: BACKGROUND: In 1994, acrylamide (AA) was classified as a probable human carcinogen by the International Agency for Research on Cancer. In 2002, AA was discovered at relatively high concentrations in some starchy, plant-based foods cooked at high temperatures. PATIENTS AND METHODS: A prospective analysis was conducted to evaluate the association between the dietary intake of AA and ductal adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox regression modeling. EPIC includes >500,000 men and women aged 35-75 at enrollment from 10 European countries. AA intake was estimated for each participant by combining questionnaire-based food consumption data with a harmonized AA database derived from the EU monitoring database of AA levels in foods, and evaluated in quintiles and continuously. RESULTS: After a mean follow-up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were observed and included in the present analysis. At baseline, the mean dietary AA intake in EPIC was 26.22 µg/day. No overall association was found between continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95, 95%CI:0.89-1.01 per 10 µg/day). There was no effect measure modification by smoking status, sex, diabetes, alcohol intake or geographic region. However, there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 µg/day) between AA intake and PC risk in obese persons as defined using the body mass index (BMI, ≥ 30 kg/m(2)), but not when body fatness was defined using waist and hip circumference or their ratio. CONCLUSIONS: Dietary intake of AA was not associated with an increased risk of PC in the EPIC cohort.

23 Article Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. 2013

Michaud, Dominique S / Izard, Jacques / Wilhelm-Benartzi, Charlotte S / You, Doo-Ho / Grote, Verena A / Tjønneland, Anne / Dahm, Christina C / Overvad, Kim / Jenab, Mazda / Fedirko, Veronika / Boutron-Ruault, Marie Christine / Clavel-Chapelon, Françoise / Racine, Antoine / Kaaks, Rudolf / Boeing, Heiner / Foerster, Jana / Trichopoulou, Antonia / Lagiou, Pagona / Trichopoulos, Dimitrios / Sacerdote, Carlotta / Sieri, Sabina / Palli, Domenico / Tumino, Rosario / Panico, Salvatore / Siersema, Peter D / Peeters, Petra H M / Lund, Eiliv / Barricarte, Aurelio / Huerta, José-María / Molina-Montes, Esther / Dorronsoro, Miren / Quirós, J Ramón / Duell, Eric J / Ye, Weimin / Sund, Malin / Lindkvist, Björn / Johansen, Dorthe / Khaw, Kay-Tee / Wareham, Nick / Travis, Ruth C / Vineis, Paolo / Bueno-de-Mesquita, H Bas / Riboli, Elio. ·Department of Epidemiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island, USA. ·Gut · Pubmed #22990306.

ABSTRACT: OBJECTIVE: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study. DESIGN: We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index. RESULTS: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83). CONCLUSIONS: Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.

24 Article Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort. 2012

Grote, V A / Kaaks, R / Nieters, A / Tjønneland, A / Halkjær, J / Overvad, K / Skjelbo Nielsen, M R / Boutron-Ruault, M C / Clavel-Chapelon, F / Racine, A / Teucher, B / Becker, S / Pischon, T / Boeing, H / Trichopoulou, A / Cassapa, C / Stratigakou, V / Palli, D / Krogh, V / Tumino, R / Vineis, P / Panico, S / Rodríguez, L / Duell, E J / Sánchez, M-J / Dorronsoro, M / Navarro, C / Gurrea, A B / Siersema, P D / Peeters, P H M / Ye, W / Sund, M / Lindkvist, B / Johansen, D / Khaw, K-T / Wareham, N / Allen, N E / Travis, R C / Fedirko, V / Jenab, M / Michaud, D S / Chuang, S-C / Romaguera, D / Bueno-de-Mesquita, H B / Rohrmann, S. ·Division of Cancer Epidemiology (c020), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg 69120, Germany. ·Br J Cancer · Pubmed #22617158.

ABSTRACT: BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce. METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-α (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models. RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR=1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR=1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI. CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer.

25 Article Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study. 2012

Romaguera, Dora / Vergnaud, Anne-Claire / Peeters, Petra H / van Gils, Carla H / Chan, Doris S M / Ferrari, Pietro / Romieu, Isabelle / Jenab, Mazda / Slimani, Nadia / Clavel-Chapelon, Françoise / Fagherazzi, Guy / Perquier, Florence / Kaaks, Rudolf / Teucher, Birgit / Boeing, Heiner / von Rüsten, Anne / Tjønneland, Anne / Olsen, Anja / Dahm, Christina C / Overvad, Kim / Quirós, José Ramón / Gonzalez, Carlos A / Sánchez, María José / Navarro, Carmen / Barricarte, Aurelio / Dorronsoro, Miren / Khaw, Kay-Tee / Wareham, Nicholas J / Crowe, Francesca L / Key, Timothy J / Trichopoulou, Antonia / Lagiou, Pagona / Bamia, Christina / Masala, Giovanna / Vineis, Paolo / Tumino, Rosario / Sieri, Sabina / Panico, Salvatore / May, Anne M / Bueno-de-Mesquita, H Bas / Büchner, Frederike L / Wirfält, Elisabet / Manjer, Jonas / Johansson, Ingegerd / Hallmans, Göran / Skeie, Guri / Benjaminsen Borch, Kristin / Parr, Christine L / Riboli, Elio / Norat, Teresa. ·Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. d.romaguera-bosch@imperial.ac.uk ·Am J Clin Nutr · Pubmed #22592101.

ABSTRACT: BACKGROUND: In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN: The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS: Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION: Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.

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