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Pancreatic Neoplasms: HELP
Articles by Gloria M. Petersen
Based on 120 articles published since 2009
(Why 120 articles?)
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Between 2009 and 2019, G. Petersen wrote the following 120 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial Intercepting Pancreatic Cancer: Our Dream Team's Resolve to Stop Pancreatic Cancer. 2018

Goggins, Michael G / Lippman, Scott M / Constantinou, Pamela E / Jacks, Tyler / Petersen, Gloria M / Syngal, Sapna / Maitra, Anirban. ·Division of Hematology/Oncology, Department of Medicine, Moores Center for Personalized Cancer Therapy, University of California, San Diego, La Jolla, CA. · Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX. · Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN. ·Pancreas · Pubmed #30325853.

ABSTRACT: -- No abstract --

2 Editorial Overweight, obesity, and pancreatic cancer: beyond risk alone. 2009

McWilliams, Robert R / Petersen, Gloria M. · ·JAMA · Pubmed #19549978.

ABSTRACT: -- No abstract --

3 Review Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review. 2018

Antwi, Samuel O / Petersen, Gloria M. · ·Pancreas · Pubmed #29424808.

ABSTRACT: Many risk factors have been firmly established for pancreatic cancer (PC), but the molecular processes by which known risk factors influence susceptibility to PC are not clear. There has been a recent upsurge of interest in the role of telomere length (TL), the protective DNA sequence repeats at chromosome ends, in pancreatic carcinogenesis. Given this heightened interest, we performed an in-depth, focused, and up-to-date review of the epidemiological evidence linking leukocyte TL (LTL) with PC risk. We searched MEDLINE, Embase, and the Cochrane Library databases for all published studies on LTL and PC risk, up to May 2017. Five studies were identified for review: 4 nested case-control studies and 1 retrospective case-control study. Two studies found opposite associations between LTL and PC risk: 1 found a dose-response positive association and the other found a dose-response inverse association. Two studies also found a "U-shaped" association, whereas another reported a weak nonlinear relationship. We offer potential reasons for the conflicting findings including variation in study design, biospecimen characteristics, and differences in interlaboratory measurements of TL. Future studies should carefully control for risk factors of PC that are associated also with telomere attrition and investigate the role of genetic variation in TL maintenance.

4 Review Familial pancreatic cancer. 2016

Petersen, Gloria M. ·Department of Health Sciences Research, Mayo Clinic Cancer Center, Rochester, MN. Electronic address: Petersen.gloria@mayo.edu. ·Semin Oncol · Pubmed #27899186.

ABSTRACT: Familial pancreatic cancer (FPC) includes those kindreds that contain at least two first-degree relatives with pancreatic ductal adenocarcinoma. At least 12 known hereditary syndromes or genes are associated with increased risk of developing pancreatic cancer, the foremost being BRCA2 and CDKN2A. Research into the identification of mutations in known cancer predisposition genes and through next-generation sequencing has revealed extensive heterogeneity. The development of genetic panel testing has enabled genetic risk assessment and predisposition testing to be routinely offered. Precision oncology has opened the possibility of "incidental" germline mutations that may have implications for family members. However, in both cases, evidence-based recommendations for managing patients and at-risk family members in light of genetic status remain emergent, with current practice based on expert opinion.

5 Review Familial Pancreatic Adenocarcinoma. 2015

Petersen, Gloria M. ·Department of Health Sciences Research, Mayo Clinic Cancer Center, Mayo Clinic, Charlton 6-243, Rochester, MN 55905, USA. Electronic address: Petersen.gloria@mayo.edu. ·Hematol Oncol Clin North Am · Pubmed #26226902.

ABSTRACT: Familial pancreatic cancer (FPC) kindreds have at least 2 first-degree relatives with pancreatic ductal adenocarcinoma. Studies of FPC have focused on the discovery of genetic cause and on the management of those at genetically high risk. Research reveals that a half dozen known hereditary syndromes or genes are associated with increased risk of developing pancreatic cancer, the most prominent of which are BRCA2 and CDKN2A. Genetic risk assessment and testing is already available. Owing to limited experience worldwide, guidance is often based on expert opinion, although all agree that research is needed to improve the shaping of options.

6 Review Gene-by-Environment Interactions in Pancreatic Cancer: Implications for Prevention. 2015

Jansen, Rick J / Tan, Xiang-Lin / Petersen, Gloria M. ·Department of Public Health Sciences, University of Chicago Biological Sciences, Chicago, Illinois. · Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey ; Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. ·Yale J Biol Med · Pubmed #26029010.

ABSTRACT: Pancreatic cancer (PC) has been estimated to have higher incidence and correspondingly higher mortality rates in more developed regions worldwide. Overall, the age-adjusted incidence rate is 4.9/10(5) and age-adjusted mortality rate is at 4.8/10(5). We review here our current knowledge of modifiable risk factors (cigarette smoking, obesity, diet, and alcohol) for PC, genetic variants implicated by genome-wide association studies, possible genetic interactions with risk factors, and prevention strategies to provide future research directions that may further our understanding of this complex disease. Cigarette smoking is consistently associated with a two-fold increased PC risk. PC associations with dietary intake have been largely inconsistent, with the potential exception of certain unsaturated fatty acids decreasing risk and well-done red meat or meat mutagens increasing risk. There is strong evidence to support that obesity (and related measures) increase risk of PC. Only the heaviest alcohol drinkers seem to be at an increased risk of PC. Currently, key prevention strategies include avoiding tobacco and excessive alcohol consumption and adopting a healthy lifestyle. Screening technologies and PC chemoprevention are likely to become more sophisticated, but may only apply to those at high risk. Risk stratification may be improved by taking into account gene environment interactions. Research on these modifiable risk factors is key to reducing the incidence of PC and understanding who in the population can be considered high risk.

7 Review Early detection of sporadic pancreatic cancer: summative review. 2015

Chari, Suresh T / Kelly, Kimberly / Hollingsworth, Michael A / Thayer, Sarah P / Ahlquist, David A / Andersen, Dana K / Batra, Surinder K / Brentnall, Teresa A / Canto, Marcia / Cleeter, Deborah F / Firpo, Matthew A / Gambhir, Sanjiv Sam / Go, Vay Liang W / Hines, O Joe / Kenner, Barbara J / Klimstra, David S / Lerch, Markus M / Levy, Michael J / Maitra, Anirban / Mulvihill, Sean J / Petersen, Gloria M / Rhim, Andrew D / Simeone, Diane M / Srivastava, Sudhir / Tanaka, Masao / Vinik, Aaron I / Wong, David. ·From the *Department of Medicine, Mayo Clinic, Rochester, MN; †Department of Biomedical Engineering, University of Virginia, Charlottesville, VA; Departments of ‡Biochemistry and Molecular Biology, §Pathology and Microbiology, and ∥Surgery, Fred & Pamela Buffett Cancer Center, University of Nebraska, Omaha, NE; ¶Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD; #Division of Gastroenterology, University of Washington, Seattle, WA; **Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD; ††Sawgrass Leadership Institute, Ponte Vedra Beach, FL; ‡‡Department of Surgery, University of Utah, Salt Lake City, UT; §§Department of Radiology, Stanford University School of Medicine, Stanford; ∥∥Department of Medicine, David Geffen School of Medicine, and ¶¶General Surgery, University of California Los Angeles, Los Angeles, CA; ##Kenner Family Research Fund; ***Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY; †††Department of Internal Medicine, University of Greifswald, Greifswald, Germany; ‡‡‡Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX; §§§Department of Health Sciences Research, Mayo Clinic, Rochester, MN; ∥∥∥Gastroenterology Division, Department of Internal Medicine and Comprehensive Cancer Center, and ¶¶¶Department of Surgery, School of Medicine, University of Michigan, Ann Arbor, MI; ###Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Rockville, MD; ****Departments of Surgery and Oncology, Kyushu University, Fukuoka, Japan; ††††Department of Medicine, Eastern Virginia Medical School, Norfolk, VA; and ‡‡‡‡Division of Oral Biology and Medicine, CLA School of Dentistry, Jonnson Comprehensive Cancer Center, University of California Los Angeles, L ·Pancreas · Pubmed #25931254.

ABSTRACT: Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

8 Clinical Trial The vitamin D receptor gene as a determinant of survival in pancreatic cancer patients: Genomic analysis and experimental validation. 2018

Innocenti, Federico / Owzar, Kouros / Jiang, Chen / Etheridge, Amy S / Gordân, Raluca / Sibley, Alexander B / Mulkey, Flora / Niedzwiecki, Donna / Glubb, Dylan / Neel, Nicole / Talamonti, Mark S / Bentrem, David J / Seiser, Eric / Yeh, Jen Jen / Van Loon, Katherine / McLeod, Howard / Ratain, Mark J / Kindler, Hedy L / Venook, Alan P / Nakamura, Yusuke / Kubo, Michiaki / Petersen, Gloria M / Bamlet, William R / McWilliams, Robert R. ·UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, United States of America. · Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, United States of America. · Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, United States of America. · North Shore University Health System, Evanston, IL, United States of America. · Northwestern University, Chicago, IL, United States of America. · University of California at San Francisco, San Francisco, CA, United States of America. · Moffitt Cancer Center, Tampa, FL, United States of America. · University of Chicago, Chicago, IL, United States of America. · Center for Genomic Medicine, RIKEN, Yokohama, Japan. · Mayo Clinic, Rochester, MN, United States of America. ·PLoS One · Pubmed #30107003.

ABSTRACT: PURPOSE: Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) in patients after treatment with gemcitabine using genome-wide screens of germline DNA. We aim also to support these findings with in vitro functional analysis. PATIENTS AND METHODS: Genome-wide screens of germline DNA in two independent cohorts of pancreatic cancer patients (from the Cancer and Leukemia Group B (CALGB) 80303 and the Mayo Clinic) were used to select new genes associated with OS. The vitamin D receptor gene (VDR) was selected, and the interactions of genetic variation in VDR with circulating vitamin D levels and gemcitabine treatment were evaluated. Functional effects of common VDR variants were also evaluated in experimental assays in human cell lines. RESULTS: The rs2853564 variant in VDR was associated with OS in patients from both the Mayo Clinic (HR 0.81, 95% CI 0.70-0.94, p = 0.0059) and CALGB 80303 (HR 0.74, 0.63-0.87, p = 0.0002). rs2853564 interacted with high pre-treatment levels of 25-hydroxyvitamin D (25(OH)D, a measure of endogenous vitamin D) (p = 0.0079 for interaction) and with gemcitabine treatment (p = 0.024 for interaction) to confer increased OS. rs2853564 increased transcriptional activity in luciferase assays and reduced the binding of the IRF4 transcription factor. CONCLUSION: Our findings propose VDR as a novel determinant of survival in advanced pancreatic cancer patients. Common functional variation in this gene might interact with endogenous vitamin D and gemcitabine treatment to determine improved patient survival. These results support evidence for a modulatory role of the vitamin D pathway for the survival of advanced pancreatic cancer patients.

9 Clinical Trial Mutations in the pancreatic secretory enzymes 2018

Tamura, Koji / Yu, Jun / Hata, Tatsuo / Suenaga, Masaya / Shindo, Koji / Abe, Toshiya / MacGregor-Das, Anne / Borges, Michael / Wolfgang, Christopher L / Weiss, Matthew J / He, Jin / Canto, Marcia Irene / Petersen, Gloria M / Gallinger, Steven / Syngal, Sapna / Brand, Randall E / Rustgi, Anil / Olson, Sara H / Stoffel, Elena / Cote, Michele L / Zogopoulos, George / Potash, James B / Goes, Fernando S / McCombie, Richard W / Zandi, Peter P / Pirooznia, Mehdi / Kramer, Melissa / Parla, Jennifer / Eshleman, James R / Roberts, Nicholas J / Hruban, Ralph H / Klein, Alison Patricia / Goggins, Michael. ·Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Health Sciences Research, Mayo Clinic, Rochester, MN 55905. · Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada M5G 1X5. · Population Sciences Division, Dana-Farber Cancer Institute, Boston, MA 02215. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213. · Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Pancreatic Cancer Translational Center of Excellence, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10017. · Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109. · Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201. · The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada H3H 2R9. · The Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada H3A 1A3. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. · InGenious Targeting Laboratory, Ronkonkoma, NY 11779. · Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; mgoggins@jhmi.edu. ·Proc Natl Acad Sci U S A · Pubmed #29669919.

ABSTRACT: To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of

10 Article Altered exocrine function can drive adipose wasting in early pancreatic cancer. 2018

Danai, Laura V / Babic, Ana / Rosenthal, Michael H / Dennstedt, Emily A / Muir, Alexander / Lien, Evan C / Mayers, Jared R / Tai, Karen / Lau, Allison N / Jones-Sali, Paul / Prado, Carla M / Petersen, Gloria M / Takahashi, Naoki / Sugimoto, Motokazu / Yeh, Jen Jen / Lopez, Nicole / Bardeesy, Nabeel / Fernandez-Del Castillo, Carlos / Liss, Andrew S / Koong, Albert C / Bui, Justin / Yuan, Chen / Welch, Marisa W / Brais, Lauren K / Kulke, Matthew H / Dennis, Courtney / Clish, Clary B / Wolpin, Brian M / Vander Heiden, Matthew G. ·Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. · Mayo Clinic, Rochester, MN, USA. · Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · University of California San Diego School of Medicine, La Jolla, CA, USA. · Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. · MD Anderson, Department of Radiation Oncology, Houston, TX, USA. · Stanford Cancer Institute, Stanford, CA, USA. · David Geffen School of Medicine at University of California, Los Angeles, CA, USA. · Section of Hematology/Oncology, Boston University and Boston Medical Center, Boston, MA, USA. · Broad Institute of MIT and Harvard University, Cambridge, MA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. bwolpin@partners.org. · Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. mvh@mit.edu. · Dana-Farber Cancer Institute, Boston, MA, USA. mvh@mit.edu. · Broad Institute of MIT and Harvard University, Cambridge, MA, USA. mvh@mit.edu. ·Nature · Pubmed #29925948.

ABSTRACT: Malignancy is accompanied by changes in the metabolism of both cells and the organism

11 Article Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer. 2018

Hu, Chunling / Hart, Steven N / Polley, Eric C / Gnanaolivu, Rohan / Shimelis, Hermela / Lee, Kun Y / Lilyquist, Jenna / Na, Jie / Moore, Raymond / Antwi, Samuel O / Bamlet, William R / Chaffee, Kari G / DiCarlo, John / Wu, Zhong / Samara, Raed / Kasi, Pashtoon M / McWilliams, Robert R / Petersen, Gloria M / Couch, Fergus J. ·Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. · Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida. · Qiagen Sciences Research and Development, Qiagen Inc, Hilden, Germany. · Department of Medicine, Mayo Clinic, Jacksonville, Florida. · Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota. ·JAMA · Pubmed #29922827.

ABSTRACT: Importance: Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined. Objective: To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer. Design, Setting, and Participants: Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123 136 individuals with exome sequence data in the public Genome Aggregation Database and 53 105 in the Exome Aggregation Consortium database. Exposures: Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer. Main Outcomes and Measures: Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction-based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls. Results: Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05). Conclusions and Relevance: In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations.

12 Article Model to Determine Risk of Pancreatic Cancer in Patients With New-Onset Diabetes. 2018

Sharma, Ayush / Kandlakunta, Harika / Nagpal, Sajan Jiv Singh / Feng, Ziding / Hoos, William / Petersen, Gloria M / Chari, Suresh T. ·Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. · Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Pancreatic Cancer Action Network, Manhattan Beach, California. · Department of Health Science Research, Mayo Clinic, Rochester, Minnesota. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address: chari.suresh@mayo.edu. ·Gastroenterology · Pubmed #29775599.

ABSTRACT: BACKGROUND & AIMS: Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a model to determine risk of PC in patients with NOD. METHODS: We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epidemiology Project from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for 3 factors identified in the discovery cohort to be most strongly associated with PC (64 patients with PC and 192 with type 2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1,096 patients with diabetes; of these, 9 patients (82%) had PC within 3 years of meeting the criteria for NOD. RESULTS: In the discovery cohort, the END-PAC model identified patients who developed PC within 3 years of diabetes onset (area under receiver operating characteristic curve 0.87); a score of at least 3 identified patients who developed PC with 80% sensitivity and specificity. In the validation cohort, a score of at least 3 identified 7 of 9 patients with PC (78%) with 85% specificity; the prevalence of PC in patients with a score of at least 3 (3.6%) was 4.4-fold greater than in patients with NOD. A high END-PAC score in patients who did not have PC (false positives) was often due to such factors as recent steroid use or different malignancy. An ENDPAC score no higher than 0 (in 49% of patients) meant that patients had an extremely low risk for PC. An END-PAC score of at least 3 identified 75% of patients in the discovery cohort more than 6 months before a diagnosis of PC. CONCLUSIONS: Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of PC in patients with NOD based on glycemic status (END-PAC model). An independent prospective study is needed to further validate this model, which could contribute to early detection of PC.

13 Article Attitudes Toward Return of Genetic Research Results to Relatives, Including After Death: Comparison of Cancer Probands, Blood Relatives, and Spouse/Partners. 2018

Radecki Breitkopf, Carmen / Wolf, Susan M / Chaffee, Kari G / Robinson, Marguerite E / Lindor, Noralane M / Gordon, Deborah R / Koenig, Barbara A / Petersen, Gloria M. ·1 Mayo Clinic, Rochester, MN, USA. · 2 University of Minnesota, Minneapolis, MN, USA. · 3 Mayo Clinic, Scottsdale, AZ, USA. · 4 University of California, San Francisco, CA, USA. ·J Empir Res Hum Res Ethics · Pubmed #29701109.

ABSTRACT: Genetic research generates results with implications for relatives. Recommendations addressing relatives' access to a participant's genetic research findings include eliciting participant preferences about access and choosing a representative to make decisions about access upon participant incapacity/death. Representatives are likely to be blood relatives or spouse/partners (who may share genetically related children). This raises the question of whether relatives hold similar attitudes about access or divergent attitudes that may yield conflict. We surveyed pancreatic cancer biobank participants (probands) and relatives in a family registry (blood relatives and spouse/partners of probands); 1,903 (>55%) surveys were returned. Results revealed few attitudinal differences between the groups. A slightly higher proportion of blood relatives agreed with statements reflecting proband privacy. In conclusion, probands' decisions on access are likely to be accepted by relatives; in choosing a representative, probands may not face major differences in attitudes about privacy/sharing between a blood relative and a spouse/partner.

14 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

15 Article Decreased Skeletal Muscle Volume Is a Predictive Factor for Poorer Survival in Patients Undergoing Surgical Resection for Pancreatic Ductal Adenocarcinoma. 2018

Sugimoto, Motokazu / Farnell, Michael B / Nagorney, David M / Kendrick, Michael L / Truty, Mark J / Smoot, Rory L / Chari, Suresh T / Moynagh, Michael R / Petersen, Gloria M / Carter, Rickey E / Takahashi, Naoki. ·Department of Surgery, Division of Subspecialty General Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. · Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. · Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. · Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. · Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. takahashi.naoki@mayo.edu. ·J Gastrointest Surg · Pubmed #29392613.

ABSTRACT: BACKGROUND: The aim of this study was to investigate the impact of decreased skeletal muscle (SM) volume on survival outcomes in patients undergoing surgical resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: Between March 2000 and February 2015, 323 patients who underwent upfront surgical resection for PDAC were identified from the Mayo Clinic SPORE in Pancreatic Cancer. Body composition data, including SM area, subcutaneous adipose tissue area, and visceral adipose tissue area were calculated using an abdominal computed tomography (CT) image at the third lumbar spinal level. The body composition data were normalized by patients' height (e.g., SM index, cm RESULTS: Because the median SM index was significantly different between males vs. females (49.9 cm CONCLUSIONS: A smaller sex-standardized SM index is a predictive factor for shorter overall and recurrence-free survival in PDAC patients undergoing surgery.

16 Article Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history. 2018

Chaffee, Kari G / Oberg, Ann L / McWilliams, Robert R / Majithia, Neil / Allen, Brian A / Kidd, John / Singh, Nanda / Hartman, Anne-Renee / Wenstrup, Richard J / Petersen, Gloria M. ·Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. · Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA. · Myriad Genetics Laboratories, Inc., Salt Lake City, Utah, USA. ·Genet Med · Pubmed #28726808.

ABSTRACT: PurposePanel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germ-line mutations. However, small sample sizes or number of genes evaluated limit prevalence estimates of these mutations. We estimated prevalence of mutations in PDAC patients with positive family history.MethodsWe sequenced 25 cancer susceptibility genes in lymphocyte DNA from 302 PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreatic Research Registry. Kindreds containing at least two first-degree relatives with PDAC met criteria for familial pancreatic cancer (FPC), while the remaining were familial, but not FPC.ResultsThirty-six patients (12%) carried at least one deleterious mutation in one of 11 genes. Of FPC patients, 25/185 (14%) were carriers, while 11/117 (9%) non-FPC patients with family history were carriers. Deleterious mutations (n) identified in PDAC patients were BRCA2 (11), ATM (8), CDKN2A (4), CHEK2 (4), MUTYH/MYH (3 heterozygotes, not biallelic), BRCA1 (2), and 1 each in BARD1, MSH2, NBN, PALB2, and PMS2. Novel mutations were found in ATM, BARD1, and PMS2.ConclusionMultiple susceptibility gene testing in PDAC patients with family history of pancreatic cancer is warranted regardless of FPC status and will inform genetic risk counseling for families.

17 Article The spectrum of genetic variants in hereditary pancreatic cancer includes Fanconi anemia genes. 2018

Slavin, Thomas P / Neuhausen, Susan L / Nehoray, Bita / Niell-Swiller, Mariana / Solomon, Ilana / Rybak, Christina / Blazer, Kathleen / Adamson, Aaron / Yang, Kai / Sand, Sharon / Guerrero-Llamas, Nancy / Castillo, Danielle / Herzog, Josef / Wu, Xiwei / Tao, Shu / Raja, Shivali / Chung, Vincent / Singh, Gagandeep / Nadesan, Sue / Brown, Sandra / Cruz-Correa, Marcia / Petersen, Gloria M / Weitzel, Jeffrey / Anonymous671109. ·Department of Population Sciences, City of Hope National Medical Center, 1500 E. Duarte Rd, Bldg. 173, Duarte, CA, 91010, USA. tslavin@coh.org. · Division of Clinical Cancer Genetics, Department of Medical Oncology, City of Hope National Medical Center, 1500 E. Duarte Rd, Bldg. 173, Room # 131, Duarte, CA, 91010, USA. tslavin@coh.org. · Department of Population Sciences, City of Hope National Medical Center, 1500 E. Duarte Rd, Bldg. 173, Duarte, CA, 91010, USA. · HealthQuest, Dyson Center for Cancer Care, 45 Reade Place, Poughkeepsie, NY, 12603, USA. · Department of Molecular and Cellular Biology, City of Hope National Medical Center, 1500 E. Duarte Rd, Duarte, CA, 91010, USA. · Division of Clinical Cancer Genetics, Department of Medical Oncology, City of Hope National Medical Center, 1500 E. Duarte Rd, Bldg. 173, Room # 131, Duarte, CA, 91010, USA. · Department of Surgery, City of Hope National Medical Center, 1500 E. Duarte Rd, Duarte, CA, 91010, USA. · Harrington Cancer Center, 1500 Wallace Blvd, Amarillo, TX, 79106, USA. · St. Joseph Hospital, 1100 W Stewart Dr., Orange, CA, 92868, USA. · University of Puerto Rico, Paseo Dr. Jose Celso Barbosa, San Juan, 00921, Puerto Rico. · Mayo Clinic, 216 2nd St. SW, Rochester, MN, 55902, USA. ·Fam Cancer · Pubmed #28687971.

ABSTRACT: Approximately 5-10% of all pancreatic cancer patients carry a predisposing mutation in a known susceptibility gene. Since >90% of patients present with late stage disease, it is crucial to identify high risk individuals who may be amenable to early detection or other prevention. To explore the spectrum of hereditary pancreatic cancer susceptibility, we evaluated germline DNA from pancreatic cancer participants (n = 53) from a large hereditary cancer registry. For those without a known predisposition mutation gene (n = 49), germline next generation sequencing was completed using targeted capture for 706 candidate genes. We identified 16 of 53 participants (30%) with a pathogenic (P) or likely pathogenic (LP) variant that may be related to their hereditary pancreatic cancer predisposition; seven had mutations in genes associated with well-known cancer syndromes (13%) [ATM (2), BRCA2 (3), MSH2 (1), MSH6 (1)]. Many had mutations in Fanconi anemia complex genes [BRCA2 (3 participants), FANCF, FANCM]. Eight participants had rare protein truncating variants of uncertain significance with no other P or LP variants. Earlier age of pancreatic cancer diagnosis (57.5 vs 64.8 years) was indicative of possessing a P or LP variant, as was cancer family history (p values <0.0001). Our multigene panel approach for identifying known cancer predisposing genetic susceptibility in those at risk for hereditary pancreatic cancer may have direct applicability to clinical practice in cases with mutations in actionable genes. Future pancreatic cancer predisposition studies should include evaluation of the Fanconi anemia genes.

18 Article Characterising 2018

Zhang, Mingfeng / Lykke-Andersen, Soren / Zhu, Bin / Xiao, Wenming / Hoskins, Jason W / Zhang, Xijun / Rost, Lauren M / Collins, Irene / Bunt, Martijn van de / Jia, Jinping / Parikh, Hemang / Zhang, Tongwu / Song, Lei / Jermusyk, Ashley / Chung, Charles C / Zhu, Bin / Zhou, Weiyin / Matters, Gail L / Kurtz, Robert C / Yeager, Meredith / Jensen, Torben Heick / Brown, Kevin M / Ongen, Halit / Bamlet, William R / Murray, Bradley A / McCarthy, Mark I / Chanock, Stephen J / Chatterjee, Nilanjan / Wolpin, Brian M / Smith, Jill P / Olson, Sara H / Petersen, Gloria M / Shi, Jianxin / Amundadottir, Laufey. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA. · Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA. · Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA. · Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, FDA, Jefferson, Missouri, USA. · Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, Maryland, USA. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Oxford Centre for Diabetes, Endocrinology & Metabolism, University of Oxford, Oxford, UK. · Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA. · Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York, USA. · Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. · Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, USA. · The Eli and Edythe L Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, Cambridge, Massachusetts, USA. · Oxford NIHR Biomedical Research Centre, Churchill Hospital, Headington, Oxford, UK. · Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. · Division of Gastroenterology and Hepatology, Georgetown University Hospital, Washington, D.C., USA. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York City, New York, USA. ·Gut · Pubmed #28634199.

ABSTRACT: OBJECTIVE: To elucidate the genetic architecture of gene expression in pancreatic tissues. DESIGN: We performed expression quantitative trait locus (eQTL) analysis in histologically normal pancreatic tissue samples (n=95) using RNA sequencing and the corresponding 1000 genomes imputed germline genotypes. Data from pancreatic tumour-derived tissue samples (n=115) from The Cancer Genome Atlas were included for comparison. RESULTS: We identified 38 615 CONCLUSIONS: We have identified

19 Article Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. 2017

Cohen, Joshua D / Javed, Ammar A / Thoburn, Christopher / Wong, Fay / Tie, Jeanne / Gibbs, Peter / Schmidt, C Max / Yip-Schneider, Michele T / Allen, Peter J / Schattner, Mark / Brand, Randall E / Singhi, Aatur D / Petersen, Gloria M / Hong, Seung-Mo / Kim, Song Cheol / Falconi, Massimo / Doglioni, Claudio / Weiss, Matthew J / Ahuja, Nita / He, Jin / Makary, Martin A / Maitra, Anirban / Hanash, Samir M / Dal Molin, Marco / Wang, Yuxuan / Li, Lu / Ptak, Janine / Dobbyn, Lisa / Schaefer, Joy / Silliman, Natalie / Popoli, Maria / Goggins, Michael G / Hruban, Ralph H / Wolfgang, Christopher L / Klein, Alison P / Tomasetti, Cristian / Papadopoulos, Nickolas / Kinzler, Kenneth W / Vogelstein, Bert / Lennon, Anne Marie. ·The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Howard Hughes Medical Institute, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Sidney Kimmel Cancer Center at Johns Hopkins, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. · Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Division of Systems Biology and Personalized Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3021, Australia. · Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC 3010, Australia. · Department of Medical Oncology, Western Health, Melbourne, VIC 3021, Australia. · Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202. · Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. · Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065. · Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15260. · Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260. · Department of Epidemiology, Mayo Clinic, Rochester, MN 55902. · Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. · Department of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea. · Division of Pancreatic Surgery, Department of Surgery, San Raffaele Scientific Institute Research Hospital, 20132 Milan, Italy. · Department of Pathology, San Raffaele Scientific Institute Research Hospital, 20132 Milan, Italy. · The Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. · Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. · Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · Department of Epidemiology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205. · Division of Biostatistics and Bioinformatics, Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287. · The Ludwig Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287; bertvog@gmail.com amlennon@jhmi.edu. · The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21287; bertvog@gmail.com amlennon@jhmi.edu. ·Proc Natl Acad Sci U S A · Pubmed #28874546.

ABSTRACT: The earlier diagnosis of cancer is one of the keys to reducing cancer deaths in the future. Here we describe our efforts to develop a noninvasive blood test for the detection of pancreatic ductal adenocarcinoma. We combined blood tests for

20 Article Detection of early pancreatic ductal adenocarcinoma with thrombospondin-2 and CA19-9 blood markers. 2017

Kim, Jungsun / Bamlet, William R / Oberg, Ann L / Chaffee, Kari G / Donahue, Greg / Cao, Xing-Jun / Chari, Suresh / Garcia, Benjamin A / Petersen, Gloria M / Zaret, Kenneth S. ·Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, 9-131 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA. · Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. · Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. · Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. · Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Abramson Cancer Center (Tumor Biology Program), Perelman School of Medicine, University of Pennsylvania, 9-131 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-5157, USA. zaret@upenn.edu. ·Sci Transl Med · Pubmed #28701476.

ABSTRACT: Markers are needed to facilitate early detection of pancreatic ductal adenocarcinoma (PDAC), which is often diagnosed too late for effective therapy. Starting with a PDAC cell reprogramming model that recapitulated the progression of human PDAC, we identified secreted proteins and tested a subset as potential markers of PDAC. We optimized an enzyme-linked immunosorbent assay (ELISA) using plasma samples from patients with various stages of PDAC, from individuals with benign pancreatic disease, and from healthy controls. A phase 1 discovery study (

21 Article Differential and Joint Effects of Metformin and Statins on Overall Survival of Elderly Patients with Pancreatic Adenocarcinoma: A Large Population-Based Study. 2017

E, Jian-Yu / Lu, Shou-En / Lin, Yong / Graber, Judith M / Rotter, David / Zhang, Lanjing / Petersen, Gloria M / Demissie, Kitaw / Lu-Yao, Grace / Tan, Xiang-Lin. ·Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey. · Department of Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey. · Department of Biostatistics, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, New Jersey. · Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, New Jersey. · Department of Pathology, University Medical Center of Princeton, Plainsboro, New Jersey. · Department of Biological Sciences, Rutgers, The State University of New Jersey, Newark, New Jersey. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. · Department of Medical Oncology, Sidney Kimmel Cancer Center at Jefferson, Sidney Kimmel Medical College, Philadelphia, Pennsylvania. · Sidney Kimmel Cancer Center at Jefferson, Philadelphia, Pennsylvania. · Jefferson College of Population Health, Philadelphia, Pennsylvania. · Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey. tanxi@cinj.rutgers.edu. · Department of Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey. ·Cancer Epidemiol Biomarkers Prev · Pubmed #28619830.

ABSTRACT:

22 Article Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer. 2017

Andersen, Dana K / Korc, Murray / Petersen, Gloria M / Eibl, Guido / Li, Donghui / Rickels, Michael R / Chari, Suresh T / Abbruzzese, James L. ·Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. · Division of Endocrinology, Department of Medicine, and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, and Indiana University Melvin and Bren Simon Cancer Center and Pancreatic Cancer Signature Center, Indianapolis, IN. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN. · Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. · Department of Gastrointestinal Medical Oncology, MD Anderson Cancer Center, Houston, TX. · Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. · Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN. · Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC james.abbruzzese@duke.edu. ·Diabetes · Pubmed #28507210.

ABSTRACT: The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association's 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.

23 Article Association between Alcohol Consumption, Folate Intake, and Risk of Pancreatic Cancer: A Case-Control Study. 2017

Yallew, Winta / Bamlet, William R / Oberg, Ann L / Anderson, Kristin E / Olson, Janet E / Sinha, Rashmi / Petersen, Gloria M / Stolzenberg-Solomon, Rachael Z / Jansen, Rick J. ·Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. Bamlet.William4@mayo.edu. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. Oberg.Ann@mayo.edu. · Department of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA. ander116@umn.edu. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. Olson.Janet@mayo.edu. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20850, USA. sinhar@mail.nih.gov. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. Petersen.Gloria@mayo.edu. · Department of Epidemiology, National Institutes of Health, Bethesda, MD 20850, USA. Rachael.Solomon@nih.gov. · Department of Public Health, North Dakota State University, Fargo, ND 58102, USA. rick.jansen@ndsu.edu. ·Nutrients · Pubmed #28468303.

ABSTRACT: Pancreatic cancer is one of the most fatal common cancers affecting both men and women, representing about 3% of all new cancer cases in the United States. In this study, we aimed to investigate the association of pancreatic cancer risk with alcohol consumption as well as folate intake. We performed a case-control study of 384 patients diagnosed with pancreatic cancer from May 2004 to December 2009 and 983 primary care healthy controls in a largely white population (>96%). Our findings showed no significant association between risk of pancreatic cancer and either overall alcohol consumption or type of alcohol consumed (drinks/day). Our study showed dietary folate intake had a modest effect size, but was significantly inversely associated with pancreatic cancer (odds ratio (OR) = 0.99, p < 0.0001). The current study supports the hypothesis that pancreatic cancer risk is reduced with higher food-based folate intake.

24 Article Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148. 2017

Fang, Jun / Jia, Jinping / Makowski, Matthew / Xu, Mai / Wang, Zhaoming / Zhang, Tongwu / Hoskins, Jason W / Choi, Jiyeon / Han, Younghun / Zhang, Mingfeng / Thomas, Janelle / Kovacs, Michael / Collins, Irene / Dzyadyk, Marta / Thompson, Abbey / O'Neill, Maura / Das, Sudipto / Lan, Qi / Koster, Roelof / Anonymous1061269 / Anonymous1071269 / Anonymous1081269 / Stolzenberg-Solomon, Rachael S / Kraft, Peter / Wolpin, Brian M / Jansen, Pascal W T C / Olson, Sara / McGlynn, Katherine A / Kanetsky, Peter A / Chatterjee, Nilanjan / Barrett, Jennifer H / Dunning, Alison M / Taylor, John C / Newton-Bishop, Julia A / Bishop, D Timothy / Andresson, Thorkell / Petersen, Gloria M / Amos, Christopher I / Iles, Mark M / Nathanson, Katherine L / Landi, Maria Teresa / Vermeulen, Michiel / Brown, Kevin M / Amundadottir, Laufey T. ·Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. · Department of Molecular Biology, Radboud Institute for Molecular Life Sciences, Radboud University, Nijmegen 6500 HB, The Netherlands. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, 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 21702, USA. · Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire 03756, USA. · Protein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA. · Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. · Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. · Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA. · Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York City, New York 10065, USA. · Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. · Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK. · Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK. · Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA. · Translational Medicine and Human Genetics, Department of Medicine and Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ·Nat Commun · Pubmed #28447668.

ABSTRACT: Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.

25 Article Genetically Predicted Telomere Length is not Associated with Pancreatic Cancer Risk. 2017

Antwi, Samuel O / Bamlet, William R / Broderick, Brendan T / Chaffee, Kari G / Oberg, Ann / Jatoi, Aminah / Boardman, Lisa A / Petersen, Gloria M. ·Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. · Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. · Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota. · Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. · Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. petersen.gloria@mayo.edu. ·Cancer Epidemiol Biomarkers Prev · Pubmed #28264873.

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