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Pancreatic Neoplasms: HELP
Articles by Harvey A. Risch
Based on 52 articles published since 2009
(Why 52 articles?)
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Between 2009 and 2019, H. Risch wrote the following 52 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Review Current Approaches to Pancreatic Cancer Screening. 2019

Chhoda, Ankit / Lu, Lingeng / Clerkin, Barbara M / Risch, Harvey / Farrell, James J. ·Yale Waterbury Internal Medicine Program, Yale School of Medicine, New Haven, Connecticut. · Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. · Pancreatic Disease Program, Yale School of Medicine, New Haven, Connecticut. · Yale Center for Pancreatic Diseases, Yale School of Medicine, New Haven, Connecticut; Yale Center for Pancreatic Diseases, Department of Digestive Diseases, Yale School of Public Health, New Haven, Connecticut. Electronic address: james.j.farrell@yale.edu. ·Am J Pathol · Pubmed #30558719.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of only 8% and is estimated to be the second leading cause of cancer-related deaths by 2021. Prior convention held that screening for PDAC would not be beneficial; however, a deeper understanding of the carcinogenesis pathway supports a potential window of opportunity among the target population. Screening for PDAC is not a standard practice among the general population because of its low incidence. However, screening may be beneficial for individuals with familial history, chronic diseases with genetic predispositions, or inherited cancer syndromes, such as hereditary breast ovarian cancer syndrome, hereditary pancreatitis, Peutz-Jeghers syndrome, familial atypical multiple mole melanoma, Lynch syndrome (hereditary nonpolyposis colorectal cancer), ataxia telangiectasia, and Li-Fraumeni syndrome, all of which have been associated with an increased risk of developing PDAC. The screening strategies among these high-risk individuals are targeted to identify precursor lesions and PDAC at an early resectable stage. This review describes the risk factors for pancreatic cancer, especially the genetic risk factors in high-risk individuals and current screening strategies available for PDAC.

2 Review Exosomes: potential for early detection in pancreatic cancer. 2016

Lu, Lingeng / Risch, Harvey A. ·Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale School of Medicine, Yale Cancer Center, New Haven, CT 06520-8034, USA. ·Future Oncol · Pubmed #26860951.

ABSTRACT: Progress in the treatment of patients with pancreatic cancer at earlier stages has motivated research in identifying novel noninvasive or minimally invasive biomarkers for early detection. Exosomes, which contain bioactive molecules (such as proteins, RNAs and lipids), are membrane-structured nanovesicles that are secreted from living cells and are found in human body fluids. As functional mediators, exosomes play key roles in cell-cell communications, regulating diverse biological processes. Here we aim to examine recent findings in the potential diagnostic value of serum exosomes in pancreatic cancer.

3 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

4 Article Impact of Sixteen Established Pancreatic Cancer Susceptibility Loci in American Jews. 2017

Streicher, Samantha A / Klein, Alison P / Olson, Sara H / Amundadottir, Laufey T / DeWan, Andrew T / Zhao, Hongyu / Risch, Harvey A. ·Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. · Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut. · Program of Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. harvey.risch@yale.edu. ·Cancer Epidemiol Biomarkers Prev · Pubmed #28754795.

ABSTRACT:

5 Article Aspirin Use and Reduced Risk of Pancreatic Cancer. 2017

Risch, Harvey A / Lu, Lingeng / Streicher, Samantha A / Wang, Jing / Zhang, Wei / Ni, Quanxing / Kidd, Mark S / Yu, Herbert / Gao, Yu-Tang. ·Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. harvey.risch@yale.edu. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. · Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. · Wren Laboratories LLC, Branford, Connecticut. · Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii. ·Cancer Epidemiol Biomarkers Prev · Pubmed #27999143.

ABSTRACT: BACKGROUND: Few options besides the avoidance of smoking and obesity are available to prevent pancreatic cancer. The association between aspirin use and risk of pancreatic cancer has been inconsistent across studies. METHODS: We performed a population-based study of 761 case and 794 control subjects frequency matched on sex and age during 2006 to 2011 in Shanghai, China. Participants were asked about episodes of regular use of aspirin, tablets per day or week, and ages that the use started and stopped. Data were analyzed by unconditional logistic regression, with adjustments for age, sex, education, body mass index, years of cigarette smoking, cigarettes smoked per day, Helicobacter pylori CagA seropositivity, ABO blood group, and history of diabetes mellitus. Meta-regression was carried out to summarize the literature. RESULTS: Ever-regular use of aspirin was associated with lowered risk of pancreatic cancer: OR = 0.54; 95% confidence interval (CI), 0.40-0.73; P = 10 CONCLUSIONS: Regular use of aspirin thus appears to reduce risk of pancreatic cancer by almost half. IMPACT: People who take aspirin for prevention of other diseases likely also reduce their risk of pancreatic cancer. Aside from benefits for both cardiovascular disease and certain cancers, long-term aspirin use entails some risks of bleeding complications, which necessitates risk-benefit analysis for individual decisions about use. Cancer Epidemiol Biomarkers Prev; 26(1); 68-74. ©2016 AACR.

6 Article Nonsteroidal anti-inflammatory drugs, statins, and pancreatic cancer risk: a population-based case-control study. 2016

Kho, Pik Fang / Fawcett, Jonathan / Fritschi, Lin / Risch, Harvey / Webb, Penelope M / Whiteman, David C / Neale, Rachel E. ·Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia. · School of Medicine, University of Queensland, Brisbane, Australia. · School of Public Health, Curtin University, Perth, Australia. · School of Public Health, Yale University, New Haven, CT, USA. · School of Public Health, University of Queensland, Brisbane, Australia. · Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia. Rachel.Neale@qimrberghofer.edu.au. · School of Public Health, University of Queensland, Brisbane, Australia. Rachel.Neale@qimrberghofer.edu.au. ·Cancer Causes Control · Pubmed #27817122.

ABSTRACT: PURPOSE: Studies suggest that aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and statins may reduce risk of some cancers. However, findings have been conflicting as to whether these agents reduce the risk of pancreatic cancer. METHODS: We used data from the Queensland Pancreatic Cancer Study, a population-based case-control study. In total, 704 cases and 711 age- and sex-matched controls were recruited. Participants completed an interview in which they were asked about history of NSAID and statin use. We included 522 cases and 653 controls who had completed the medication section of the interview in this analysis. Unconditional multivariable logistic regression was used to estimate associations between medication use and pancreatic cancer. RESULTS: We found no consistent evidence of an association between use of NSAIDs or statins and risk of pancreatic cancer. There was some suggestion of a protective effect in infrequent users of selective COX-2 inhibitors, but no association in more frequent users. We did not find evidence of protective effects in analyses stratified by sex, smoking status, time between diagnosis and interview, or presence/absence of metastases. CONCLUSIONS: Overall, our results do support the hypothesis that use of NSAIDs or statins may reduce the odds of developing pancreatic cancer.

7 Article Association between family cancer history and risk of pancreatic cancer. 2016

Schulte, Annaka / Pandeya, Nirmala / Fawcett, Jonathan / Fritschi, Lin / Klein, Kerenaftali / Risch, Harvey A / Webb, Penelope M / Whiteman, David C / Neale, Rachel E. ·Department of Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia; School of Medicine, University of Queensland, 288 Herston Road, Herston, Queensland 4006, Australia. Electronic address: Annaka.Schulte@qimrberghofer.edu.au. · Department of Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia; School of Population Health, Level 2, Population Health Building, 887 Mayne Road, University of Queensland, Herston, Queensland 4006, Australia. · Department of Population Health, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia. · School of Public Health, Curtin University, Kent Street, Bentley, Perth, Western Australia 6102, Australia. · Yale School of Public Health, 60 College St, New Haven, CT 06510, United States. ·Cancer Epidemiol · Pubmed #27810486.

ABSTRACT: PURPOSE: Family history of pancreatic adenocarcinoma is an established risk factor for the disease. However, associations of pancreatic cancer with other familial cancers are less clear. We analyzed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, to investigate associations between family history of various cancer types and risk of pancreatic cancer. MATERIALS AND METHODS: Our study included 591 pancreatic cancer patients and 646 controls, all of whom self-reported the histories of cancer in their first-degree relatives. We used logistic regression to estimate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Based on our results, we conducted a systematic literature review using the Medline (OVID) database to identify articles pertaining to the association between family history of melanoma and risk of pancreatic cancer. A meta-analysis including associations in five published studies, unpublished results from a study co-author and the QPCS results was then performed using the DerSimonian and Laird random-effects model. RESULTS: Cases were more likely than controls to report a family history of pancreatic cancer (OR 2.20, 95% CI 1.16-4.19) and melanoma (OR 1.74, 95% CI 1.03-2.95), but not of breast, ovarian, respiratory, other gastrointestinal or prostate cancer. Meta-analysis of melanoma family history and pancreatic cancer risk yielded an OR of 1.22 (95% CI 1.00-1.51). CONCLUSIONS: Our results yield further evidence of increased risk of pancreatic cancer in those with family histories of the disease. We also provide suggestive evidence of an association between family history of melanoma and risk of pancreatic cancer.

8 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.

9 Article Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study. 2016

Childs, Erica J / Chaffee, Kari G / Gallinger, Steven / Syngal, Sapna / Schwartz, Ann G / Cote, Michele L / Bondy, Melissa L / Hruban, Ralph H / Chanock, Stephen J / Hoover, Robert N / Fuchs, Charles S / Rider, David N / Amundadottir, Laufey T / Stolzenberg-Solomon, Rachael / Wolpin, Brian M / Risch, Harvey A / Goggins, Michael G / Petersen, Gloria M / Klein, Alison P. ·Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota. · Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada. · Population Sciences Division, Dana-Farber Cancer Institute, and Gastroenterology Division, Brigham and Women's Hospital, Boston, Massachusetts. · Department of Oncology, Karmanos Cancer Institute and Wayne State University, Detroit, Michigan. · Baylor College of Medicine, Dan L. Duncan Cancer Center, Houston, Texas. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut. · Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. · Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland. Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland. aklein1@jhmi.edu. ·Cancer Epidemiol Biomarkers Prev · Pubmed #27197284.

ABSTRACT: Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 × 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 × 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 × 10(-5)) to pancreatic cancer for SNPs at HDAC9 (7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 25(7); 1185-91. ©2016 AACR.

10 Article Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis From the International Pancreatic Cancer Case-Control Consortium (PanC4). 2016

Lujan-Barroso, Leila / Zhang, Wei / Olson, Sara H / Gao, Yu-Tang / Yu, Herbert / Baghurst, Peter A / Bracci, Paige M / Bueno-de-Mesquita, H Bas / Foretová, Lenka / Gallinger, Steven / Holcatova, Ivana / Janout, Vladimír / Ji, Bu-Tian / Kurtz, Robert C / La Vecchia, Carlo / Lagiou, Pagona / Li, Donghui / Miller, Anthony B / Serraino, Diego / Zatonski, Witold / Risch, Harvey A / Duell, Eric J. ·From the *Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; †Department of Epidemiology, Shanghai Cancer Institute and Jiao Tong University, Shanghai, China; ‡Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; §Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI; ∥Public Health, Women's and Children's Hospital, Adelaide, SA, Australia; ¶University of California, San Francisco, San Francisco, CA; #National Institute for Public Health and the Environment (RIVM), Bilthoven; **Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands; ††Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; ‡‡Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; §§Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Institute and MF MU, Brno, Czech Republic; ∥∥University Health Network, Department of Surgery, University of Toronto, Toronto, Canada; ¶¶Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague; ##Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic; ***National Cancer Institute, Bethesda, MD; †††Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; ‡‡‡Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; §§§Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Greece; ∥∥∥Department of Epidemiology, Harvard School of Public Health, Boston, MA; ¶¶¶M.D. Anderson Cancer Center, University of Texas, Houston, TX; ###Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; ****Unit of Epidemiology and Biostatistics, CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; ††††Cancer Center and Institute of Oncology, Warsaw, Poland; and ‡‡‡‡Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT. ·Pancreas · Pubmed #27088489.

ABSTRACT: OBJECTIVES: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC). METHODS: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates. RESULTS: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84). CONCLUSIONS: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary.

11 Article Risk Factors for Early-Onset and Very-Early-Onset Pancreatic Adenocarcinoma: A Pancreatic Cancer Case-Control Consortium (PanC4) Analysis. 2016

McWilliams, Robert R / Maisonneuve, Patrick / Bamlet, William R / Petersen, Gloria M / Li, Donghui / Risch, Harvey A / Yu, Herbert / Fontham, Elizabeth T H / Luckett, Brian / Bosetti, Cristina / Negri, Eva / La Vecchia, Carlo / Talamini, Renato / Bueno de Mesquita, H Bas / Bracci, Paige / Gallinger, Steven / Neale, Rachel E / Lowenfels, Albert B. ·From the *Department of Oncology, Mayo Clinic, Rochester, MN; †Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy; ‡Division of Biostatistics, Mayo Clinic; §Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥Department of Gastrointestinal Medical Oncology, UT MD Anderson Cancer Center, Houston, TX; ¶Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT; #Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI; **Louisiana State University School of Public Health, New Orleans, LA; ††Tulane School of Public Health, New Orleans, LA; ‡‡Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," and §§Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; ∥∥S.O.C. Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy; ¶¶National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; School of Public Health, Imperial College London, London, United Kingdom; ##Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; ***Division of General Surgery, University of Toronto, Toronto, Ontario, Canada; †††Cancer and Population Studies Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia; and ‡‡‡Department of Surgery, Department of Family Medicine, New York Medical College, Valhalla, NY. ·Pancreas · Pubmed #26646264.

ABSTRACT: OBJECTIVES: While pancreatic cancer (PC) most often affects older adults, to date, there has been no comprehensive assessment of risk factors among PC patients younger than 60 years. METHODS: We defined early-onset PC (EOPC) and very-early-onset PC (VEOPC) as diagnosis of PC in patients younger than 60 and 45 years, respectively. We pooled data from 8 case-control studies, including 1954 patients with EOPC and 3278 age- and sex-matched control subjects. Logistic regression analysis was performed to identify associations with EOPC and VEOPC. RESULTS: Family history of PC, diabetes mellitus, smoking, obesity, and pancreatitis were associated with EOPC. Alcohol use equal to or greater than 26 g daily also was associated with increased risk of EOPC (odds ratio, 1.49; 95% confidence interval, 1.21-1.84), and there appeared to be a dose- and age-dependent effect of alcohol on risk. The point estimate for risk of VEOPC was an odds ratio of 2.18 (95% confidence interval, 1.17-4.09). CONCLUSIONS: The established risk factors for PC, including smoking, diabetes, family history of PC, and obesity, also apply to EOPC. Alcohol intake appeared to have an age-dependent effect; the strongest association was with VEOPC.

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

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

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

13 Article Detectable Symptomatology Preceding the Diagnosis of Pancreatic Cancer and Absolute Risk of Pancreatic Cancer Diagnosis. 2015

Risch, Harvey A / Yu, Herbert / Lu, Lingeng / Kidd, Mark S. · ·Am J Epidemiol · Pubmed #26049860.

ABSTRACT: The survival duration for pancreatic cancer is short. Given its low lifetime risk (1.5%), established factors for the disease have insufficient specificity to identify individuals at high risk of nonfamilial cancer, and prediagnostic signs and symptoms are vague and not limited to pancreatic causes. We considered whether statistical models that incorporated both risk factors and prediagnosis symptomatology could improve prediction enough to provide practical risk estimates. We combined US Surveillance Epidemiology and End Results (SEER) incidence data from 2008 to 2010 with regression models from representative case-control data from Connecticut (2005-2009) to estimate age- and sex-specific 5-year absolute risks of pancreatic cancer diagnosis. Our risk model included current cigarette smoking (adjusted odds ratio (OR) = 3.3, 95% confidence interval (CI): 2.1, 5.0), current use of proton pump-inhibitor antiheartburn medications (OR = 6.2, 95% CI: 1.7, 23), recent diagnosis of diabetes mellitus (OR = 4.8, 95% CI: 2.2, 11), recent diagnosis of pancreatitis (OR = 19, 95% CI: 3.1, 120), Jewish ancestry (OR = 1.8, 95% CI: 1.1, 3.1), and ABO blood group other than O (OR = 1.3, 95% CI: 1.0, 1.8). In total, 0.87% of controls with combinations of these factors had estimated 5-year absolute risks greater than 5%, and for some, the risks reached more than 10%. Combining risk factors for pancreatic cancer with detectable prediagnostic symptomatology can allow investigators to begin to identify small segments of the population with risks sufficiently high enough to make screening efforts among them potentially useful.

14 Article Vitamin D and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium. 2015

Waterhouse, M / Risch, H A / Bosetti, C / Anderson, K E / Petersen, G M / Bamlet, W R / Cotterchio, M / Cleary, S P / Ibiebele, T I / La Vecchia, C / Skinner, H G / Strayer, L / Bracci, P M / Maisonneuve, P / Bueno-de-Mesquita, H B / Zaton Ski, W / Lu, L / Yu, H / Janik-Koncewicz, K / Polesel, J / Serraino, D / Neale, R E / Anonymous1990830. ·Division of Population Health, QIMR Berghofer Medical Research Institute, Herston Centre for Research Excellence in Sun and Health, Queensland University of Technology, Kelvin Grove, Australia. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, USA. · Department of Epidemiology, IRCCS-Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy. · Division of Epidemiology and Community Health, University of Minnesota, Minneapolis. · Department of Health Sciences Research, Mayo Clinic, Rochester, USA. · Prevention and Cancer Control, Cancer Care Ontario, Toronto Dalla Lana School of Public Health, University of Toronto, Toronto. · Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto Department of Surgery, University of Toronto, Toronto, Canada. · Division of Population Health, QIMR Berghofer Medical Research Institute, Herston. · Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. · Truven Health Analytics, Durham. · Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, USA. · Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy. · National Institute for Public Health and the Environment, Bilthoven Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK. · Department of Epidemiology, The Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. · Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA. · Division of Population Health, QIMR Berghofer Medical Research Institute, Herston Centre for Research Excellence in Sun and Health, Queensland University of Technology, Kelvin Grove, Australia rachel.neale@qimrberghofer.edu.au. ·Ann Oncol · Pubmed #25977560.

ABSTRACT: BACKGROUND: The potential role of vitamin D in the aetiology of pancreatic cancer is unclear, with recent studies suggesting both positive and negative associations. PATIENTS AND METHODS: We used data from nine case-control studies from the International Pancreatic Cancer Case-Control Consortium (PanC4) to examine associations between pancreatic cancer risk and dietary vitamin D intake. Study-specific odds ratios (ORs) were estimated using multivariable logistic regression, and ORs were then pooled using a random-effects model. From a subset of four studies, we also calculated pooled estimates of association for supplementary and total vitamin D intake. RESULTS: Risk of pancreatic cancer increased with dietary intake of vitamin D [per 100 international units (IU)/day: OR = 1.13, 95% confidence interval (CI) 1.07-1.19, P = 7.4 × 10(-6), P-heterogeneity = 0.52; ≥230 versus <110 IU/day: OR = 1.31, 95% CI 1.10-1.55, P = 2.4 × 10(-3), P-heterogeneity = 0.81], with the association possibly stronger in people with low retinol/vitamin A intake. CONCLUSION: Increased risk of pancreatic cancer was observed with higher levels of dietary vitamin D intake. Additional studies are required to determine whether or not our finding has a causal basis.

15 Article Association between Helicobacter pylori and pancreatic cancer risk: a meta-analysis. 2015

Schulte, Annaka / Pandeya, Nirmala / Fawcett, Jonathan / Fritschi, Lin / Risch, Harvey A / Webb, Penelope M / Whiteman, David C / Neale, Rachel E. ·Department of Population Health, Royal Brisbane Hospital, QIMR Berghofer Medical Research Institute, Locked Bag 2000, Brisbane, QLD, Australia, Annaka.Schulte@qimrberghofer.edu.au. ·Cancer Causes Control · Pubmed #25951801.

ABSTRACT: PURPOSE: Gastric colonization with Helicobacter pylori (H. pylori) has been implicated in the pathogenesis of pancreatic cancer, but results of epidemiological studies have been inconclusive. We analyzed data from the Queensland Pancreatic Cancer Study, an Australian population-based case-control study, and incorporated our findings into an updated meta-analysis. METHODS: Blood samples were obtained from 580 patients and 626 controls, and enzyme-linked immunosorbent assay kits were used to determine seropositivity to H. pylori and its virulence protein, cytotoxin-associated gene A (CagA). Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using logistic regression. Results were incorporated into a meta-analysis along with results of studies identified through systematic literature review. Adjusted ORs and 95 % CIs were calculated using the DerSimonian and Laird random-effects model. RESULTS: No overall association was observed between H. pylori seropositivity and risk of pancreatic cancer (OR 1.00; 95 % CI 0.74-1.35). Nonsignificantly decreased pancreatic cancer risk was observed with CagA seropositivity (OR 0.74; 95 % CI 0.48-1.15) and increased risk with CagA-negative H. pylori seropositivity (OR 1.23; 95 % CI 0.83-1.82). Ten studies were included in the meta-analysis. There was no significant overall association between H. pylori seropositivity and pancreatic cancer risk (OR 1.13; 95 % CI 0.86-1.50), but evidence of CagA strain-specific associations (OR 0.78; 95 % CI 0.67-0.91 and OR 1.30; 95 % CI 1.02-1.65 for CagA-positive and CagA-negative strains, respectively). CONCLUSIONS: Our results provide further evidence for the existence of strain-specific associations between H. pylori and pancreatic cancer.

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

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

ABSTRACT: A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.

17 Article 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.

18 Article Occupational exposure to N-nitrosamines and pesticides and risk of pancreatic cancer. 2015

Fritschi, Lin / Benke, Geza / Risch, Harvey A / Schulte, Annaka / Webb, Penelope M / Whiteman, David C / Fawcett, Jonathan / Neale, Rachel E. ·School of Public Health, Curtin University, Perth, Western Australia, Australia. · Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia. · Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA. · Department of Population Health, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia. · Princess Alexandra Hospital, Brisbane, Queensland, Australia. ·Occup Environ Med · Pubmed #25780030.

ABSTRACT: OBJECTIVES: Animal evidence shows that N-nitrosamines and similar xenobiotic compounds are pancreatic carcinogens. We aimed to determine whether occupational exposure to N-nitrosamines or to pesticides increases risk of pancreatic cancer development. METHODS: Participants (504 cases, 643 controls) in a population-based case-control study (The Queensland Pancreatic Cancer Study) provided data on demographic, medical and lifestyle factors and lifetime job histories. Specific questions were asked regarding work in rubber and leather industries, metalworking jobs and occupational or direct use of pesticides on animals or crops. An occupational hygienist reviewed this information (blind to case status) to assess likelihood of exposure to N-nitrosamines and pesticides, and estimated level and frequency of such exposures. RESULTS: No associations were found for risk of pancreatic cancer and occupational exposure to N-nitrosamines (OR=0.85, 95% CI 0.51 to 1.42) and no associations were seen with level or frequency of exposure. No associations were observed for ever exposure to pesticides in general (OR=0.90, 95% CI 0.61 to 1.33) or to any of the pesticide subgroups. Stratification by history of cigarette smoking did not change these results. CONCLUSIONS: This comprehensive analysis of a large case-control study does not support an association between occupational exposure to N-nitrosamines or pesticide use and risk of pancreatic cancer.

19 Article Urinary prostaglandin E2 metabolite and pancreatic cancer risk: case-control study in urban Shanghai. 2015

Zhao, Jing / Wang, Jing / Du, Jinfeng / Xu, Hongli / Zhang, Wei / Ni, Quan-Xing / Yu, Herbert / Risch, Harvey A / Gao, Yu-Tang / Gao, Ying. ·Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. · Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. · Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. · Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, United States of America. · Department of Chronic Disease Epidemiology, Yale School of Public Health and Yale Cancer Center, New Haven, CT, United States of America. ·PLoS One · Pubmed #25679523.

ABSTRACT: Pancreatic cancer has been increasing in importance in Shanghai over the last four decades. The etiology of the disease is still unclear. Evidence suggests that the COX-2 pathway, an important component of inflammation, may be involved in the disease. We aimed to evaluate the association between urinary prostaglandin E2 metabolite (PGE-M) level and risk of pancreatic cancer. From a recent population-based case-control study in Shanghai, 200 pancreatic ductal adenocarcinoma cases and 200 gender- and age- frequency matched controls were selected for the present analysis. Urinary PGE-M was measured with a liquid chromatography/mass spectrometric assay. Adjusted unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A positive association was observed between PGE-M leve and pancreatic cancer risk: OR = 1.63 (95% CI 1.01-2.63) for the third tertile compared to the first. Though the interactions were not statistically significant, the associations tended to be stronger among subjects with diabetes history (OR = 3.32; 95% CI 1.20-9.19) and higher meat intake (OR = 2.12; 95% CI 1.10-4.06). The result suggests that higher urinary PGE-M level may be associated with increased risk of pancreatic ductal adenocarcinoma.

20 Article Plasma metabolite biomarkers for the detection of pancreatic cancer. 2015

Xie, Guoxiang / Lu, Lingeng / Qiu, Yunping / Ni, Quanxing / Zhang, Wei / Gao, Yu-Tang / Risch, Harvey A / Yu, Herbert / Jia, Wei. ·Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China. ·J Proteome Res · Pubmed #25429707.

ABSTRACT: Patients with pancreatic cancer (PC) are usually diagnosed at late stages, when the disease is nearly incurable. Sensitive and specific markers are critical for supporting diagnostic and therapeutic strategies. The aim of this study was to use a metabonomics approach to identify potential plasma biomarkers that can be further developed for early detection of PC. In this study, plasma metabolites of newly diagnosed PC patients (n = 100) and age- and gender-matched controls (n = 100) from Connecticut (CT), USA, and the same number of cases and controls from Shanghai (SH), China, were profiled using combined gas and liquid chromatography mass spectrometry. The metabolites consistently expressed in both CT and SH samples were used to identify potential markers, and the diagnostic performance of the candidate markers was tested in two sample sets. A diagnostic model was constructed using a panel of five metabolites including glutamate, choline, 1,5-anhydro-d-glucitol, betaine, and methylguanidine, which robustly distinguished PC patients in CT from controls with high sensitivity (97.7%) and specificity (83.1%) (area under the receiver operating characteristic curve [AUC] = 0.943, 95% confidence interval [CI] = 0.908-0.977). This panel of metabolites was then tested with the SH data set, yielding satisfactory accuracy (AUC = 0.835; 95% CI = 0.777-0.893), with a sensitivity of 77.4% and specificity of 75.8%. This model achieved a sensitivity of 84.8% in the PC patients at stages 0, 1, and 2 in CT and 77.4% in the PC patients at stages 1 and 2 in SH. Plasma metabolic signatures show promise as biomarkers for early detection of PC.

21 Article Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer. 2014

Neale, Rachel E / Clark, Paul J / Fawcett, Jonathan / Fritschi, Lin / Nagler, Belinda N / Risch, Harvey A / Walters, Rhiannon J / Crawford, William J / Webb, Penelope M / Whiteman, David C / Buchanan, Daniel D. ·QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Electronic address: Rachel.neale@qimrberghofer.edu.au. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · University of Queensland, Brisbane, Queensland, Australia. · Curtin University, Perth, Western Australia, Australia. · Yale School of Public Health, New Haven, CT, United States. · Department of Pathology, The University of Melbourne, Carlton, 3010 Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Victoria 3010, Australia. ·Cancer Epidemiol · Pubmed #25201440.

ABSTRACT: Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Methylation of DNA may influence risk or be a marker of early disease. The aim of this study was to measure the association between methylation of three DNA repetitive elements in white blood cell (WBC) DNA and pancreatic cancer. DNA from WBCs of pancreatic cancer cases (n=559) and healthy unrelated controls (n=603) were tested for methylation of the LINE-1, Alu and Sat2 DNA repetitive elements using MethyLight quantitative PCR assays. Odds ratios (ORs) and 95% confidence intervals (95%CI) between both continuous measures of percent of methylated sample compared to a reference (PMR) or quintiles of PMR and pancreatic cancer, adjusted for age, sex, smoking, BMI, alcohol and higher education, were estimated. The PMR for each of the three markers was higher in cases than in controls, although only LINE-1 was significantly associated with pancreatic cancer (OR per log unit=1.37, 95%CI=1.16-1.63). The marker methylation score for all three markers combined was significantly associated with pancreatic cancer (p-trend=0.0006). There were no associations between measures of PMR and either presence of metastases, or timing of blood collection in relation to diagnosis, surgery, chemotherapy or death (all p>0.1). We observed an association between methylation of LINE-1 in WBC DNA and risk of pancreatic cancer. Further studies are needed to confirm this association.

22 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.

23 Article Case-control study of aspirin use and risk of pancreatic cancer. 2014

Streicher, Samantha A / Yu, Herbert / Lu, Lingeng / Kidd, Mark S / Risch, Harvey A. ·Authors' Affiliations: Department of Chronic Disease Epidemiology, Yale School of Public Health; · Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii. · Department of Surgery, Yale School of Medicine, New Haven, Connecticut; and. · Authors' Affiliations: Department of Chronic Disease Epidemiology, Yale School of Public Health; harvey.risch@yale.edu. ·Cancer Epidemiol Biomarkers Prev · Pubmed #24969230.

ABSTRACT: BACKGROUND: Pancreas-cancer prognosis is dismal, with 5-year survival less than 5%. Significant relationships between aspirin use and decreased pancreas-cancer incidence and mortality have been shown in four of 13 studies. METHODS: To evaluate further a possible association between aspirin use and risk of pancreatic cancer, we used data from a population-based Connecticut study conducted from January 2005 to August 2009, of 362 pancreas-cancer cases frequency matched to 690 randomly sampled controls. RESULTS: Overall, regular use of aspirin was associated with reduced risk of pancreatic cancer [odds ratio (OR), 0.52; 95% confidence interval (CI), 0.39-0.69]. Increments of decreasing risk of pancreatic cancer were observed for each year of low-dose or regular-dose aspirin use (OR, 0.94; 95% CI, 0.91-0.98 and OR, 0.98; 95% CI, 0.96-1.01, respectively) and for increasing years in the past that low-dose or regular-dose aspirin use had started (OR, 0.95; 95% CI, 0.92-0.99 and OR, 0.98; 95% CI, 0.96-1.00, respectively). Reduced risk of pancreatic cancer was seen in most categories of calendar time period of aspirin use, for both low-dose aspirin and regular-dose aspirin use. Relative to continuing use at the time of interview, termination of aspirin use within 2 years of interview was associated with increased risk of pancreatic cancer (OR, 3.24; 95% CI, 1.58-6.65). CONCLUSIONS: Our results provide some support that a daily aspirin regimen may reduce risk of developing pancreatic cancer. IMPACT: Long-term aspirin use has benefits for both cardiovascular disease and cancer, but appreciable bleeding complications that necessitate risk-benefit analysis for individual applications.

24 Article Cigarette smoking and pancreatic cancer risk: more to the story than just pack-years. 2014

Schulte, Annaka / Pandeya, Nirmala / Tran, Bich / Fawcett, Jonathan / Fritschi, Lin / Risch, Harvey A / Webb, Penelope M / Whiteman, David C / Neale, Rachel E / Anonymous4970782. ·Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Electronic address: Annaka.Schulte@qimrberghofer.edu.au. · Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Population Health, University of Queensland, Brisbane, Australia. · Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Western Australian Institute for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia. ·Eur J Cancer · Pubmed #24461200.

ABSTRACT: PURPOSE: Cigarette smoking is an established risk factor for pancreatic adenocarcinoma. However, few studies have thoroughly investigated the effects of independent smoking dimensions (duration, intensity, cumulative dose and time since quitting) on risk estimates. We analysed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, with the aim of determining which smoking component is primarily important to pancreatic cancer risk. METHODS: Our study included 705 pancreatic cancer patients and 711 controls. Logistic regression and generalised additive logistic regression (for non-linear dose effects) were used to determine odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Compared to never-smokers, current smokers had an increased risk of pancreatic cancer (OR=3.4; 95% CI 2.4-5.0) after adjustment for age, sex, education, alcohol intake and birth country. Of the various smoking dimensions, smoking duration and time since quitting had a greater effect on OR estimates (OR 1.3; 95% CI 1.1-1.4 and OR 0.8; 95% CI 0.7-0.8) than smoking intensity (OR 1.1; 95% CI 0.9-1.2), once ever-smoking was accounted for. CONCLUSIONS: This study confirms the association between cigarette smoking and pancreatic adenocarcinoma, and provides evidence to suggest that smoking pattern, in addition to dose effect, may affect disease risk.

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

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

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

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