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Pancreatic Neoplasms: HELP
Articles by Miquel Porta
Based on 18 articles published since 2010
(Why 18 articles?)
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Between 2010 and 2020, M. Porta wrote the following 18 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review How useful is it clinically to analyse the K-ras mutational status for the diagnosis of exocrine pancreatic cancer? A systematic review and meta-analysis. 2011

Parker, Lucy A / Lumbreras, Blanca / Lopez, Tomás / Hernández-Aguado, Ildefonso / Porta, Miquel. ·Department of Public Health, Miguel Hernández University, Alicante, Spain. ·Eur J Clin Invest · Pubmed #21391995.

ABSTRACT: BACKGROUND: More clinically meaningful diagnostic tests are needed in exocrine pancreatic cancer (EPC). K-ras mutations are the most frequently acquired genetic alteration in EPC. We analysed the diagnostic utility of detecting K-ras mutations through a systematic analysis of the literature. METHODS: We searched PubMed using suitable medical subject headings and text words. Original research articles that evaluated the diagnostic accuracy of detecting K-ras mutations for diagnosis of EPC were selected. Two investigators independently extracted data from each study regarding the methodology used, the methodological quality of the study, the diagnostic accuracy reported and the authors' conclusions about clinical applicability of the test. Combined estimates for the sensitivity and specificity of K-ras were determined using bivariate meta-analysis; heterogeneity was explored using meta-regression. RESULTS: We assessed 34 studies from 30 published articles. The research reports were prone to numerous methodological biases and often lacked vital information for assessing external validity. The sensitivity of detecting K-ras status ranged from 0% through 100%, and the specificity from 58% through 100%. Diagnostic accuracy was highest when cytohistological samples were used: sensitivity and specificity were 76·5% (66·7-84·2) and 91·8% (87·6-94·1), respectively. Studies conducted in a clinically relevant population observed lower accuracy than case-control designs (68·4% vs. 82·7%). CONCLUSIONS: Because of the numerous methodological limitations of studies, the utility of analysing K-ras mutations for the diagnosis of EPC remains unknown. Flaws in diagnostic biomarkers with well-established biological properties, as K-ras, become even more relevant when the promises of 'personalized medicine' are pondered.

2 Article Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma. 2019

Gómez-Tomás, Álvaro / Pumarega, José / Alguacil, Juan / Amaral, André F S / Malats, Núria / Pallarès, Natàlia / Gasull, Magda / Porta, Miquel / Anonymous3771118. ·School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. · Faculty of Health and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. · Universidad de Huelva, Huelva, Spain. · Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College London, London, United Kingdom. · Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. · Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain. ·Environ Mol Mutagen · Pubmed #31066938.

ABSTRACT: Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital-based controls (case-control analyses), and between 17 KRAS wild-type tumors and 61 KRAS mutated tumors (case-case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild-type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98-11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14-0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild-type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild-type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693-703, 2019. © 2019 Wiley Periodicals, Inc.

3 Article Toenail concentrations of trace elements and occupational history in pancreatic cancer. 2019

Camargo, Judit / Pumarega, José A / Alguacil, Joan / Sanz-Gallén, Pere / Gasull, Magda / Delclos, George L / Amaral, André F S / Porta, Miquel. ·School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. · Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Universidad de Huelva, Huelva, Spain. · Clinical Toxicology Unit, Hospital Clínic, Barcelona, Spain. · School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Center for Research in Occupational Health (CiSAL), Universitat Pompeu Fabra, Barcelona, Spain; The University of Texas School of Public Health, Houston, TX, USA. · Population Health and Occupational Disease, National Heart and Lung Institute, Imperial College London, London, UK. · School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address: mporta@imim.es. ·Environ Int · Pubmed #30928845.

ABSTRACT: BACKGROUND: Some occupations potentially entailing exposure to cadmium, arsenic, lead, selenium, nickel, and chromium have been associated with an increased risk of exocrine pancreatic cancer (EPC), but no studies have assessed whether body concentrations of such compounds differed among subjects occupationally exposed and unexposed. No studies which found that exposure to such metals increased the risk of EPC assessed whether past occupations were the source of exposure. OBJECTIVE: The aim was to analyse the relationship between toenail concentrations of trace elements and occupational history in EPC patients. METHODS: The study included 114 EPC cases personally interviewed on occupational history and lifestyle factors. Occupations were coded according to the International Standard Classification of Occupations 1988. Selected occupational exposures were assessed by two industrial hygienists and with the Finnish job-exposure matrix (Finjem). Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Adjusted geometric means (aGMs) and 95% confidence intervals (95% CI) were calculated. RESULTS: Patients occupationally exposed to aromatic hydrocarbon solvents (AHs) had higher concentrations of cadmium, manganese, lead, iron and vanadium. The aGM of cadmium concentrations for cases exposed to any pesticide was 0.056 μg/g [95% CI: 0.029-0.108], and, for unexposed cases, 0.023 μg/g [0.017-0.031]. Patients occupationally exposed to pesticides had higher concentrations of cadmium and manganese. Higher concentrations of vanadium, lead and arsenic were related to exposure to formaldehyde. Vanadium and lead were also associated with exposure to chlorinated hydrocarbon solvents, and arsenic was related to exposure to polycyclic aromatic hydrocarbons (PAHs). CONCLUSIONS: Patients occupationally exposed to AHs, pesticides, chlorinated hydrocarbon solvents, formaldehyde, volatile sulphur compounds and PAHs had higher concentrations of several metals. These elements may account for some of the occupational risks previously reported for pancreatic cancer.

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

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

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

5 Article Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort. 2019

Gasull, Magda / Pumarega, José / Kiviranta, Hannu / Rantakokko, Panu / Raaschou-Nielsen, Ole / Bergdahl, Ingvar A / Sandanger, Torkjel Manning / Goñi, Fernando / Cirera, Lluís / Donat-Vargas, Carolina / Alguacil, Juan / Iglesias, Mar / Tjønneland, Anne / Overvad, Kim / Mancini, Francesca Romana / Boutron-Ruault, Marie-Christine / Severi, Gianluca / Johnson, Theron / Kühn, Tilman / Trichopoulou, Antonia / Karakatsani, Anna / Peppa, Eleni / Palli, Domenico / Pala, Valeria / Tumino, Rosario / Naccarati, Alessio / Panico, Salvatore / Verschuren, Monique / Vermeulen, Roel / Rylander, Charlotta / Nøst, Therese Haugdahl / Rodríguez-Barranco, Miguel / Molinuevo, Amaia / Chirlaque, María-Dolores / Ardanaz, Eva / Sund, Malin / Key, Tim / Ye, Weimin / Jenab, Mazda / Michaud, Dominique / Matullo, Giuseppe / Canzian, Federico / Kaaks, Rudolf / Nieters, Alexandra / Nöthlings, Ute / Jeurnink, Suzanne / Chajes, Veronique / Matejcic, Marco / Gunter, Marc / Aune, Dagfinn / Riboli, Elio / Agudo, Antoni / Gonzalez, Carlos Alberto / Weiderpass, Elisabete / Bueno-de-Mesquita, Bas / Duell, Eric J / Vineis, Paolo / Porta, Miquel. ·Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. · National Institute for Health and Welfare, Department of Health Security, Kuopio, Finland. · Danish Cancer Society Research Center, Copenhagen, Denmark. · Department of Biobank Research, Umeå University, Umeå, Sweden; Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. · Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Biodonostia Health Research Institute; Public Health Laboratory in Gipuzkoa, Basque Government, San Sebastian, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain. · Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Universidad de Huelva, Huelva, Spain. · Department of Pathology, Hospital del Mar (PSMar), Barcelona, Spain. · Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. · CESP, Faculté de Médecine - Univ. Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France; Gustave Roussy, Villejuif, France. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain. · Hellenic Health Foundation, Athens, Greece. · Hellenic Health Foundation, Athens, Greece; 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, "ATTIKON" University Hospital, Haidari, Greece. · Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. · Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. · Cancer Registry and Histopathology Department, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy. · Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy. · Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. · Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. · Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Murcia Regional Health Council, IMIB - Arrixaca, Murcia, Spain; Department of Health and Social Sciences, University of Murcia, Murcia, Spain. · CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. · Department of Biobank Research, Umeå University, Umeå, Sweden; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden. · Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), Lyon, France. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Department Medical Sciences, University of Torino, Italian Institute for Genomic Medicine -IIGM/HuGeF, Torino, Italy. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Center for Chronic Immunodeficiency, Molecular Epidemiology, University Medical Center Freiburg, Freiburg, Germany. · Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany. · Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. · Unit of Nutrition and Cancer, Catalan Institute of Oncology (ICO-Idibell), Barcelona, Spain. · Department of Community Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Medical Epidemiology and Biostatistics Karolinska Institutet, Stockholm, Sweden; Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Genetic Epidemiology Group, Folkhälsan Research Center, Faculty of Medicine, University of Helsinki, Helsinki, Finland. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Molecular and Genetic Epidemiology Unit, Italian Institute for Genomic Medicine (IIGM), Turin, Italy; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. · Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Catalonia, Spain; Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. Electronic address: mporta@imim.es. ·Environ Res · Pubmed #30529143.

ABSTRACT: BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

6 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

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 The Association of Recently Diagnosed Diabetes and Long-term Diabetes With Survival in Pancreatic Cancer Patients: A Pooled Analysis. 2018

Jeon, Christie Y / Li, Donghui / Cleary, Sean / Stolzenberg-Solomon, Rachael / Bosetti, Cristina / La Vecchia, Carlo / Porta, Miquel / Toriola, Adetunji T / Hung, Rayjean J / Kurtz, Robert C / Olson, Sara H. · ·Pancreas · Pubmed #29401167.

ABSTRACT: OBJECTIVES: It is unclear whether long-standing diabetes or new-onset pancreatogenic diabetes contributes to poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We investigated the influence of diabetes diagnosed shortly before PDAC and long-term diabetes on overall survival in 2792 PDAC patients who had participated in 3 PDAC case-control studies in the Pancreatic Cancer Case-Control Consortium. There were 300 patients with long-term diabetes of more than 3 years' duration (11%) and 418 patients with recently diagnosed diabetes of 3-year duration or less (15%). We performed Cox regression to determine the association of long-term diabetes and recently diagnosed diabetes with overall survival, adjusting for study site, age, sex, race, stage of disease, surgery, chemotherapy, smoking history, and body mass index at diagnosis. RESULTS: In the overall population, neither long-term diabetes (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.97-1.26) nor recently diagnosed diabetes (HR, 1.06; 95% CI, 0.94-1.18) was associated with shorter survival. When stratified by stage of disease, long-term diabetes was associated with 42% increase in rate of death in persons with resectable PDAC (HR, 1.42; 95% CI, 1.13-1.78), whereas it was not associated with survival in PDAC patients with more advanced disease. CONCLUSION: Long-term diabetes was associated with increased rate of death in patients with resectable PDAC.

9 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.

10 Article Vitamin D metabolic pathway genes and pancreatic cancer risk. 2015

Arem, Hannah / Yu, Kai / Xiong, Xiaoqin / Moy, Kristin / Freedman, Neal D / Mayne, Susan T / Albanes, Demetrius / Arslan, Alan A / Austin, Melissa / Bamlet, William R / Beane-Freeman, Laura / Bracci, Paige / Canzian, Federico / Cotterchio, Michelle / Duell, Eric J / Gallinger, Steve / Giles, Graham G / Goggins, Michael / Goodman, Phyllis J / Hartge, Patricia / Hassan, Manal / Helzlsouer, Kathy / Henderson, Brian / Holly, Elizabeth A / Hoover, Robert / Jacobs, Eric J / Kamineni, Aruna / Klein, Alison / Klein, Eric / Kolonel, Laurence N / Li, Donghui / Malats, Núria / Männistö, Satu / McCullough, Marjorie L / Olson, Sara H / Orlow, Irene / Peters, Ulrike / Petersen, Gloria M / Porta, Miquel / Severi, Gianluca / Shu, Xiao-Ou / Visvanathan, Kala / White, Emily / Yu, Herbert / Zeleniuch-Jacquotte, Anne / Zheng, Wei / Tobias, Geoffrey S / Maeder, Dennis / Brotzman, Michelle / Risch, Harvey / Sampson, Joshua N / Stolzenberg-Solomon, Rachael Z. ·Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America. · Information Management Systems, Inc., Calverton, Maryland, United States of America. · Yale School of Public Health/Yale Cancer Center, New Haven, Connecticut, United States of America. · Departments of Population Health, Obstetrics and Gynecology (Obs/Gyn) and Environmental Medicine, New York University, New York, New York, United States of America. · Department of Epidemiology, University of Washington, Seattle, Washington, United States of America. · Department of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, United States of America. · Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Dalla Lana School of Public Health, University of Toronto; Prevention and Cancer Control, Cancer Care Ontario Toronto, Ontario, Canada. · Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada. · Cancer Epidemiology Centre, Cancer Council Victoria and Centre for MEGA Epidemiology, School of Population Health, the University of Melbourne, Melbourne, Australia. · Departments of Oncology, Pathology and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. · Cleveland Clinic, Glickman Urological and Kidney Institute, Cleveland, Ohio, United States of America. · Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America. · MD Mercy, Baltimore, Maryland, United States of America. · Department of Preventative Medicine, School of Medicine, University of Southern California, Los Angeles, California, United States of America. · Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America. · GroupHealth Research Institute, Seattle, Washington, United States of America. · University of Hawaii Cancer Center, Manoa, Hawaii, United States of America. · Molecular Pathology Program, Spanish National Cancer Research Center, Madrid, Spain. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. · Hospital del Mar Institute of Medical Research (IMIM), and School of Medicine, Barcelona Spain. · Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, United States of America. · 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, United States of America. · Westat, Rockville, Maryland, United States of America. ·PLoS One · Pubmed #25799011.

ABSTRACT: Evidence on the association between vitamin D status and pancreatic cancer risk is inconsistent. This inconsistency may be partially attributable to variation in vitamin D regulating genes. We selected 11 vitamin D-related genes (GC, DHCR7, CYP2R1, VDR, CYP27B1, CYP24A1, CYP27A1, RXRA, CRP2, CASR and CUBN) totaling 213 single nucleotide polymorphisms (SNPs), and examined associations with pancreatic adenocarcinoma. Our study included 3,583 pancreatic cancer cases and 7,053 controls from the genome-wide association studies of pancreatic cancer PanScans-I-III. We used the Adaptive Joint Test and the Adaptive Rank Truncated Product statistic for pathway and gene analyses, and unconditional logistic regression for SNP analyses, adjusting for age, sex, study and population stratification. We examined effect modification by circulating vitamin D concentration (≤50, >50 nmol/L) for the most significant SNPs using a subset of cohort cases (n = 713) and controls (n = 878). The vitamin D metabolic pathway was not associated with pancreatic cancer risk (p = 0.830). Of the individual genes, none were associated with pancreatic cancer risk at a significance level of p<0.05. SNPs near the VDR (rs2239186), LRP2 (rs4668123), CYP24A1 (rs2762932), GC (rs2282679), and CUBN (rs1810205) genes were the top SNPs associated with pancreatic cancer (p-values 0.008-0.037), but none were statistically significant after adjusting for multiple comparisons. Associations between these SNPs and pancreatic cancer were not modified by circulating concentrations of vitamin D. These findings do not support an association between vitamin D-related genes and pancreatic cancer risk. Future research should explore other pathways through which vitamin D status might be associated with pancreatic cancer risk.

11 Article Adjusting serum concentrations of organochlorine compounds by lipids and symptoms: a causal framework for the association with K-ras mutations in pancreatic cancer. 2014

López, Tomàs / Pumarega, José A / Pollack, Anna Z / Lee, Duk-Hee / Richiardi, Lorenzo / Jacobs, David R / Schisterman, Enrique F / Porta, Miquel. ·Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Facultat de Medicina, Universitat Autònoma de Barcelona, Catalonia, Spain. · Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Spain. · Epidemiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA. · Department of Preventive Medicine and Health Promotion Research Center, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. · Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and CPO-Piemonte, Torino, Italy. · Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN, USA. · Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Facultat de Medicina, Universitat Autònoma de Barcelona, Catalonia, Spain; CIBER en Epidemiología y Salud Pública (CIBERESP), Spain. Electronic address: mporta@imim.es. ·Chemosphere · Pubmed #25113205.

ABSTRACT: In clinically aggressive diseases, patients experience pathophysiological changes that often alter concentrations of lipids and environmental lipophilic factors; such changes are related to disease signs and symptoms. The aim of the study was to compare the effects of correcting for total serum lipids (TSL) and other clinical factors on the odds of mutations in the K-ras oncogene by organochlorine compounds (OCs), in logistic models, in 103 patients with exocrine pancreatic cancer (EPC) using a causal directed acyclic graph (DAG) framework. Results and likelihood of bias were discussed in the light of possible causal scenarios. The odds of K-ras mutated EPC was associated with some TSL-corrected OCs, including p,p'-DDT (p-value: 0.008) and polychlorinated biphenyl 138 (p-trend: 0.024). When OCs were not corrected by TSL, the OR of a K-ras mutation was significant for p,p'-DDT (p-trend: 0.035). Additionally adjusting for cholestatic syndrome increased the ORs of TSL-corrected OCs. When models were adjusted by the interval from first symptom to blood extraction (ISE), the ORs increased for both TSL-corrected and uncorrected OCs. Models with TSL-corrected OCs and adjusted for cholestatic syndrome or ISE yielded the highest ORs. We show that DAGs clarify the covariates necessary to minimize bias, and demonstrate scenarios under which adjustment for TSL-corrected OCs and failure to adjust for symptoms or ISE may induce bias. Models with TSL-uncorrected OCs may be biased too, and adjusting by symptoms or ISE may not control such biases. Our findings may have implications as well for studying environmental causes of other clinically aggressive diseases.

12 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. [2] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · Department of Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. · Pancreas Unit, Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Gastroenterology, Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo, Italy. · 1] Hospital del Mar Institute of Medical Research (IMIM), Barcelona, Spain. [2] Department of Epidemiology, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. [3] CIBERESP, Madrid, Spain. · 1] Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. [2] Departament de Ciències i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. · Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. · ARC-NET: Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy. · Toxicogenomics Unit, Center for Toxicology and Safety, National Institute of Public Health, Prague, Czech Republic. · Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. · Department of Digestive Tract Diseases, Medical University of Łodz, Łodz, Poland. · 1st Propaideutic Surgical Department, Hippocration University Hospital, Athens, Greece. · Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. · 1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. [2] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [3] Hellenic Health Foundation, Athens, Greece. · 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, State University of New York, Buffalo, New York, USA. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. · 1] Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA. [2] New York University Cancer Institute, New York, New York, USA. · 1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. [2]. · 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3]. · 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. [3]. ·Nat Genet · Pubmed #25086665.

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.

13 Article Relationships of hepatic and pancreatic biomarkers with the cholestatic syndrome and tumor stage in pancreatic cancer. 2012

Porta, Miquel / Pumarega, José / Guarner, Luisa / Malats, Núria / Solà, Ricard / Real, Francisco X / Anonymous3560731. ·Hospital del Mar Research Institute - IMIM, Barcelona, Catalonia, Spain. mporta@imim.es ·Biomarkers · Pubmed #22793268.

ABSTRACT: We analyzed relationships of hepatic and pancreatic biomarkers with the cholestatic syndrome and tumor stage in exocrine pancreatic cancer (N = 183). Information on laboratory tests and on signs and symptoms was obtained from medical records and patient interviews. Bilirubin, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT) and alkaline phosphatase were lower in tumor stage IV. The association was due to the relationship between cholestatic syndrome and earlier presentation of patients. There was no association between hepatic biomarkers and stage when adjusting by cholestatic syndrome. Relationships of hepatic and pancreatic biomarkers with pancreatic symptoms and tumor stage must be controlled in "-omics" and other studies using biomarkers.

14 Article Pancreatic cancer risk and levels of trace elements. 2012

Amaral, André F S / Porta, Miquel / Silverman, Debra T / Milne, Roger L / Kogevinas, Manolis / Rothman, Nathaniel / Cantor, Kenneth P / Jackson, Brian P / Pumarega, José A / López, Tomàs / Carrato, Alfredo / Guarner, Luisa / Real, Francisco X / Malats, Núria. ·Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), C/ Melchor Fernández Almagro 3, Madrid, Spain. ·Gut · Pubmed #22184070.

ABSTRACT: BACKGROUND AND AIMS: Knowledge on the aetiology of exocrine pancreatic cancer (EPC) is scant. The best established risk factor for EPC is tobacco smoking. Among other carcinogens, tobacco contains cadmium, a metal previously associated with an increased risk of EPC. This study evaluated the association between concentrations of trace elements in toenails and EPC risk. METHODS: The study included 118 EPC cases and 399 hospital controls from eastern Spain. Levels of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. OR and 95% CI, adjusted for potential confounders, were calculated using logistic regression. RESULTS: Significantly increased risks of EPC were observed among subjects whose concentrations of cadmium (OR 3.58, 95% CI 1.86 to 6.88; p(trend)=5×10(-6)), arsenic (OR 2.02, 95% CI 1.08 to 3.78; p(trend)=0.009) and lead (OR 6.26, 95% CI 2.71 to 14.47; p(trend)=3×10(-5)) were in the highest quartile. High concentrations of selenium (OR 0.05, 95% CI 0.02 to 0.15; p(trend)=8×10(-11)) and nickel (OR 0.27, 95% CI 0.12 to 0.59; p(trend)=2×10(-4)) were inversely associated with the risk of EPC. CONCLUSION: Novel associations are reported of lead, nickel and selenium toenail concentrations with pancreas cancer risk. Furthermore, the results confirm previous associations with cadmium and arsenic. These novel findings, if replicated in independent studies, would point to an important role of trace elements in pancreatic carcinogenesis.

15 Article Clinical validity of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer: a prospective study in a clinically-relevant spectrum of patients. 2011

Parker, Lucy A / Porta, Miquel / Lumbreras, Blanca / López, Tomàs / Guarner, Luisa / Hernández-Aguado, Ildefonso / Carrato, Alfredo / Corominas, Josep M / Rifà, Juli / Fernandez, Esteve / Alguacil, Joan / Malats, Núria / Real, Francisco X. ·Department of Public Health, Miguel Hernández University, Alicante, Spain. ·Eur J Epidemiol · Pubmed #21298467.

ABSTRACT: The diagnostic utility of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K-ras mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, pancreatic cysts, and cancer of the extrahepatic biliary system. Mutations in the K-ras oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K-ras mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2-84.8) and 78.0% (68.1-86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K-ras or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9-87.6) and 62.6% (72.9-87.6), respectively. In patients with mutated K-ras and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K-ras mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K-ras analysis in conjunction with other genetic and 'omics' technologies.

16 Article Relationships between occupational history and serum concentrations of organochlorine compounds in exocrine pancreatic cancer. 2011

Bosch de Basea, Magda / Porta, Miquel / Alguacil, Joan / Puigdomènech, Elisa / Gasull, Magda / Garrido, José A / López, Tomàs / Anonymous6460679. ·Clinical and Molecular Epidemiology of Cancer Unit, Institut Municipal d'Investigació Mèdica, Universitat Autònoma de Barcelona, Carrer del Dr Aiguader 88, E-08003 Barcelona, Catalonia, Spain. ·Occup Environ Med · Pubmed #21098829.

ABSTRACT: BACKGROUND: Previous studies investigating associations between occupational history and risk of exocrine pancreatic cancer (EPC) did not use biomarkers of exposure. The only two studies that measured internal concentrations of organochlorine compounds (OCs) in EPC did not analyse their relationship with occupation. OBJECTIVE: To analyse the relationship between occupational history and blood concentrations of seven OCs in patients with EPC. METHODS: Incident cases of EPC were prospectively identified, and during hospital admission were interviewed face-to-face on occupational history and life-style factors (n = 135). Occupations were coded according to the International Standard of Occupations 1988. Some occupational exposures were also assessed with the Finnish job-exposure matrix (Finjem). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection. RESULTS: Craftsmen and related trades workers had significantly higher concentrations of polychlorinated biphenyl (PCB) congeners 138, 153 and 180. Years worked in agriculture did not influence concentrations of p,p'-DDT, p,p'-DDE, hexachlorobenzene or β-hexachlorocyclohexane. Subjects who ever worked in agriculture had lower concentrations of PCBs (all p < 0.05). Occupational exposure to lead, nickel and low frequency magnetic fields was significantly associated with higher concentrations of PCBs. CONCLUSIONS: Certain occupations were associated with higher concentrations of PCBs, suggesting that these compounds may account for some increased risks found in previous studies. The lack of association between work in agriculture and concentrations of OC pesticides is consistent with occupation playing a lesser role than diet in influencing OC concentrations. Occupational studies on the relationships among exposure to industrial agents and EPC risk may need to consider adjusting for exposure to PCBs.

17 Article Occupational exposures and risk of pancreatic cancer. 2010

Santibañez, Miguel / Vioque, Jesús / Alguacil, Juan / de la Hera, Manuela García / Moreno-Osset, Eduardo / Carrato, Alfredo / Porta, Miquel / Kauppinen, Timo. ·IFIMAV-Marques de Valdecilla Foundation, Santander, Spain. ·Eur J Epidemiol · Pubmed #20640489.

ABSTRACT: The objective was to analyze the relationship between occupation (and specific occupational exposures) and risk of exocrine pancreatic cancer (EPC). We conducted a multicenter hospital-based case-control study in Eastern Spain. We included 161 incident cases of EPC (59.6% men, 94 with histological confirmation, of whom 80% had ductal adenocarcinoma). Cases were frequency-matched with 455 controls by sex, age and province of residence. Information was elicited using structured questionnaires. Occupations were coded according to the Spanish version of the International Standard Classification of Occupations 1988. Occupational exposure to a selection of carcinogenic substances was assessed with the Finnish Job-Exposure Matrix (FINJEM). Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multiple logistic regression, adjusting for sex, age, province, education, alcohol and smoking. A higher risk of EPC was associated with having worked as 'Miners, shotfirers, stone cutters and carvers', 'Machinery mechanics and fitters', 'Building trades workers' and 'Motor vehicle drivers' in men, 'Office Clerks' in women, and 'Waiters' in both sexes. Cases with ductal adenocarcinomas were more likely to have been exposed to chlorinated hydrocarbon solvents (OR = 4.1, 95% CI: 1.1-15.2, p-trend = 0.04). We also observed significant associations with exposure to 'synthetic polymer dust exposure' and 'ionizing radiation'. Suggestive increases in risk were observed for 'pesticides', 'diesel and gasoline engine exhaust', and 'hydrocarbon solvents'. Results support the hypothesis that occupational exposure to chlorinated hydrocarbon solvents is associated with exocrine pancreatic cancer.

18 Article The relative influence of diet and serum concentrations of organochlorine compounds on K-ras mutations in exocrine pancreatic cancer. 2010

Gasull, Magda / Porta, Miquel / Pumarega, José / Vioque, Jesús / Bosch de Basea, Magda / Puigdomènech, Elisa / Morales, Eva / Grimalt, Joan O / Malats, Núria. ·Institut Municipal d'Investigació Mèdica, Barcelona, Catalonia, Spain. ·Chemosphere · Pubmed #20350743.

ABSTRACT: BACKGROUND: In exocrine pancreatic cancer (EPC) mechanistic relationships may exist among some organochlorine compounds (OCs) and mutations in the K-ras oncogene, as well as among the latter and dietary factors. OBJECTIVE: To analyze (1) the relationship between food intake and serum concentrations of OCs in EPC patients and (2) the relative influence of food and OCs on the frequency of K-ras mutations in EPC. PATIENTS AND METHODS: Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission (N=135 patients with data on OCs and diet, and N=97 with additional information on K-ras status). OCs were measured by high-resolution gas chromatography with electron-capture detection. RESULTS: Consumption of milk and other dairy products was positively associated with concentrations of p,p'-DDT, PCB 138 and PCB 153 (log-transformed betas=0.652, 0.588 and 0.317, respectively; all p<0.05). When adjusted by OCs, dairy products were no longer associated with K-ras. By contrast, after adjusting by consumption of dairy products, patients with the highest concentrations of p,p'-DDT and some PCBs remained more likely to have a K-ras-mutated EPC than patients with lower concentrations (OR for upper tertile of PCB 138=5.5, 95% CI: 1.3-23.4). CONCLUSIONS: Dairy products were a source of OCs. The association between dairy products and K-ras mutations was not independent of OCs. By contrast, the association between OCs and K-ras was not confounded by dairy products. OCs may be more likely to contribute to the occurrence of K-ras mutations than nutrients contained in dairy products.