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Pancreatic Neoplasms: HELP
Articles by Björn Lindkvist
Based on 20 articles published since 2010
(Why 20 articles?)
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Between 2010 and 2020, B. Lindkvist wrote the following 20 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Endoscopic ultrasound in the diagnosis of chronic pancreatitis. 2015

Iglesias-García, Julio / Lariño-Noia, José / Lindkvist, Björn / Domínguez-Muñoz, J Enrique. · ·Rev Esp Enferm Dig · Pubmed #25824921.

ABSTRACT: Diagnosis of chronic pancreatitis (CP) remains a challenge. Endoscopic ultrasound (EUS) can be considered nowadays as the technique of choice for the morphological diagnosis of this disease. More than three or four EUS defined criteria of CP need to be present for the diagnosis of the disease. The development of the more restrictive Rosemont classification aims to standardize the criteria, assigning different values to different features but its impact on the EUS-based diagnosis of CP is debatable. A combined use of endoscopic function test and EUS has even increased the diagnostic yield. Elastography and FNA may be also of help for diagnosing CP. EUS also provides with very valuable information on the severity of the disease, giving key information that may influence in the treatment. Differential diagnosis of solid pancreatic masses in the context of a CP is also challenging, EUS plays a key role in this context. It provides with the possibility of obtaining specimens for histopathological diagnosis. Nowadays, new developed techniques associated to EUS, like elastography and contrast enhancement, are also showing promising results for the differentiating between these pancreatic lesions.

2 Review Diabetes, smoking, alcohol use, and family history of cancer as risk factors for pancreatic neuroendocrine tumors: a systematic review and meta-analysis. 2015

Haugvik, Sven-Petter / Hedenström, Per / Korsæth, Emilie / Valente, Roberto / Hayes, Alastair / Siuka, Darko / Maisonneuve, Patrick / Gladhaug, Ivar Prydz / Lindkvist, Björn / Capurso, Gabriele. ·Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway. ·Neuroendocrinology · Pubmed #25613442.

ABSTRACT: BACKGROUND AND AIMS: Risk factors for pancreatic neuroendocrine tumors (PNETs) are not well understood. The aim of this systematic review was to assess if diabetes mellitus, smoking, alcohol use, and family history of cancer are risk factors for PNETs. METHODS: MEDLINE and abstracts from the European and North American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for studies published until October 2013. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Five studies evaluating 4 individual populations were included (study accrual period 2000-2011) into the meta-analysis, involving 827 cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All studies had a case-control design and described regional series. The pooled adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p < 0.01; I(2) = 60.4%) for history of diabetes, 1.21 (95% CI: 0.92-1.58; p = 0.18; I(2) = 45.8%) for ever smoking, 1.37 (95% CI: 0.99-1.91; p = 0.06; I(2) = 0.0%) for heavy smoking, 1.09 (95% CI: 0.64-1.85; p = 0.75; I(2) = 85.2%) for ever alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I(2) = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p < 0.01; I(2) = 0.0%) for first-degree family history of cancer. CONCLUSIONS: Diabetes mellitus and first-degree family history of cancer are associated with an increased risk of sporadic PNET. There was also a trend for diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a risk factor for PNET, but there was considerable heterogeneity in the meta-analysis. These results suggest the need for a larger, homogeneous, international study for the clarification of risk factors for the occurrence of PNET.

3 Review The role of EUS in relation to other imaging modalities in the differential diagnosis between mass forming chronic pancreatitis, autoimmune pancreatitis and ductal pancreatic adenocarcinoma. 2012

Iglesias-García, Julio / Lindkvist, Björn / Lariño-Noia, José / Domínguez-Muñoz, J Enrique. ·Department of Gastroenterology and Foundation for Research in Digestive Diseases (FIENAD), Hospital Universitario de Santiago de Compostela, A Coruña, Spain. julio.iglesias.garcia@sergas.es ·Rev Esp Enferm Dig · Pubmed #22738702.

ABSTRACT: Differential diagnosis of solid pancreatic lesions remains as an important clinical challenge, mainly for the differentiation between mass forming chronic pancreatitis, autoimmune pancreatitis and pancreatic adenocarcinoma. Endoscopic ultrasound (EUS), computed tomography (CT) and magnetic resonance imaging (MRI) can all provide valuable and complementary information in this setting. Among them, EUS has the unique ability to obtain specimens for histopathological diagnosis and can therefore play a crucial role in the evaluation patients with inconclusive findings on initial examinations. Nowadays, new developed techniques associated to EUS, like elastography and contrast enhancement, have shown promising results for the differential diagnosis of these pancreatic lesions.

4 Article Risk and protective factors for the occurrence of sporadic pancreatic endocrine neoplasms. 2017

Valente, Roberto / Hayes, Alastair J / Haugvik, Sven-Petter / Hedenström, Per / Siuka, Darko / Korsæth, Emilie / Kämmerer, Daniel / Robinson, Stuart M / Maisonneuve, Patrick / Delle Fave, Gianfranco / Lindkvist, Bjorn / Capurso, Gabriele. ·Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy. · Department of General SurgeryRoyal Infirmary of Edinburgh, Edinburgh, UK. · Department of Hepato-Pancreato-Biliary SurgeryOslo University Hospital, Oslo, Norway. · Unit of GastroenterologyDepartment of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. · Department of GastroenterologyUniversity Medical Centre Ljubljana, Ljubljana, Slovenia. · Department of General and Visceral SurgeryZentralklinik Bad Berka, Bad Berka, Germany. · Department of Hepatopancreatobiliary and Transplantation SurgeryThe Freeman Hospital, Newcastle upon Tyne, UK. · Division of Epidemiology and BiostatisticsEuropean Institute of Oncology, Milan, Italy. · Digestive and Liver Disease UnitSant' Andrea Hospital, Sapienza University of Rome, Rome, Italy gabriele.capurso@gmail.com. ·Endocr Relat Cancer · Pubmed #28566532.

ABSTRACT: Pancreatic neuroendocrine neoplasms (PNENs) represent 10% of all pancreatic tumors by prevalence. Their incidence has reportedly increased over recent decades in parallel with that of pancreatic adenocarcinoma. PNENs are relatively rare, and of the few institutions that have published potential risk factors, findings have been heterogeneous. Our objective was to investigate the association between potential risk and protective factors for the occurrence of sporadic PNENs across a European population from several institutions. A multinational European case-control study was conducted to examine the association of selected environmental, family and medical exposure factors using a standardized questionnaire in face-to-face interviews. A ratio of 1:3 cases to controls were sex and age matched at each study site. Adjusted univariate and multivariate logistic regression analysis were performed for statistically significant factors. The following results were obtained: In 201 cases and 603 controls, non-recent onset diabetes (OR 2.09, CI 1.27-3.46) was associated with an increased occurrence of PNENs. The prevalence of non-recent onset diabetes was higher both in cases with metastatic disease (TNM stage III-IV) or advanced grade (G3) at the time of diagnosis. The use of metformin in combination with insulin was also associated with a more aggressive phenotype. Drinking coffee was more frequent in cases with localized disease at diagnosis. Our study concluded that non-recent onset diabetes was associated with an increased occurrence of PNENs and the combination of metformin and insulin was consistent with a more aggressive PNEN phenotype. In contrast to previous studies, smoking, alcohol and first-degree family history of cancer were not associated with PNEN occurrence.

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

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

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

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

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

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

7 Article Intake of coffee, decaffeinated coffee, or tea does not affect risk for pancreatic cancer: results from the European Prospective Investigation into Nutrition and Cancer Study. 2013

Bhoo-Pathy, Nirmala / Uiterwaal, Cuno S P M / Dik, Vincent K / Jeurnink, Suzanne M / Bech, Bodil H / Overvad, Kim / Halkjær, Jytte / Tjønneland, Anne / Boutron-Ruault, Marie-Christine / Fagherazzi, Guy / Racine, Antoine / Katzke, Verena A / Li, Kuanrong / Boeing, Heiner / Floegel, Anna / Androulidaki, Anna / Bamia, Christina / Trichopoulou, Antonia / Masala, Giovanna / Panico, Salvatore / Crosignani, Paolo / Tumino, Rosario / Vineis, Paolo / Peeters, Petra H M / Gavrilyuk, Oxana / Skeie, Guri / Weiderpass, Elisabete / Duell, Eric J / Arguelles, Marcial / Molina-Montes, Esther / Navarro, Carmen / Ardanaz, Eva / Dorronsoro, Miren / Lindkvist, Björn / Wallström, Peter / Sund, Malin / Ye, Weimin / Khaw, Kay-Tee / Wareham, Nick / Key, Timothy J / Travis, Ruth C / Duarte-Salles, Talita / Freisling, Heinz / Licaj, Idlir / Gallo, Valentina / Michaud, Dominique S / Riboli, Elio / Bueno-De-Mesquita, H Bas. ·Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; National Clinical Research Centre, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia. ·Clin Gastroenterol Hepatol · Pubmed #23756220.

ABSTRACT: BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer. METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression. RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers. CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.

8 Article Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort. 2013

Duell, Eric J / Travier, Noémie / Lujan-Barroso, Leila / Dossus, Laure / Boutron-Ruault, Marie-Christine / Clavel-Chapelon, Françoise / Tumino, Rosario / Masala, Giovanna / Krogh, Vittorio / Panico, Salvatore / Ricceri, Fulvio / Redondo, Maria Luisa / Dorronsoro, Miren / Molina-Montes, Esther / Huerta, José M / Barricarte, Aurelio / Khaw, Kay-Tee / Wareham, Nick J / Allen, Naomi E / Travis, Ruth / Siersema, Peter D / Peeters, Petra H M / Trichopoulou, Antonia / Fragogeorgi, Eirini / Oikonomou, Eleni / Boeing, Heiner / Schuetze, Madlen / Canzian, Federico / Lukanova, Annekatrin / Tjønneland, Anne / Roswall, Nina / Overvad, Kim / Weiderpass, Elisabete / Gram, Inger Torhild / Lund, Eiliv / Lindkvist, Björn / Johansen, Dorthe / Ye, Weimin / Sund, Malin / Fedirko, Veronika / Jenab, Mazda / Michaud, Dominique S / Riboli, Elio / Bueno-de-Mesquita, H Bas. ·Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. eduell@iconcologia.net ·Int J Cancer · Pubmed #23015357.

ABSTRACT: Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.99-2.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort.

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

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

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

10 Article Meat and fish consumption and risk of pancreatic cancer: results from the European Prospective Investigation into Cancer and Nutrition. 2013

Rohrmann, Sabine / Linseisen, Jakob / Nöthlings, Ute / Overvad, Kim / Egeberg, Rikke / Tjønneland, Anne / Boutron-Ruault, Marie Christine / Clavel-Chapelon, Françoise / Cottet, Vanessa / Pala, Valeria / Tumino, Rosario / Palli, Domenico / Panico, Salvatore / Vineis, Paolo / Boeing, Heiner / Pischon, Tobias / Grote, Verena / Teucher, Birigit / Khaw, Kay-Tee / Wareham, Nicholas J / Crowe, Francesca L / Goufa, Ioulia / Orfanos, Philippos / Trichopoulou, Antonia / Jeurnink, Suzanne M / Siersema, Peter D / Peeters, Petra H M / Brustad, Magritt / Engeset, Dagrun / Skeie, Guri / Duell, Eric J / Amiano, Pilar / Barricarte, Aurelio / Molina-Montes, Esther / Rodríguez, Laudina / Tormo, María-José / Sund, Malin / Ye, Weimin / Lindkvist, Björn / Johansen, Dorthe / Ferrari, Pietro / Jenab, Mazda / Slimani, Nadia / Ward, Heather / Riboli, Elio / Norat, Teresa / Bueno-de-Mesquita, H Bas. ·Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. sabine.rohrmann@ifspm.uzh.ch ·Int J Cancer · Pubmed #22610753.

ABSTRACT: Pancreatic cancer is the fourth most common cause of cancer death worldwide with large geographical variation, which implies the contribution of diet and lifestyle in its etiology. We examined the association of meat and fish consumption with risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 477,202 EPIC participants from 10 European countries recruited between 1992 and 2000 were included in our analysis. Until 2008, 865 nonendocrine pancreatic cancer cases have been observed. Calibrated relative risks (RRs) and 95% confidence intervals (CIs) were computed using multivariable-adjusted Cox hazard regression models. The consumption of red meat (RR per 50 g increase per day = 1.03, 95% CI = 0.93-1.14) and processed meat (RR per 50 g increase per day = 0.93, 95% CI = 0.71-1.23) were not associated with an increased pancreatic cancer risk. Poultry consumption tended to be associated with an increased pancreatic cancer risk (RR per 50 g increase per day = 1.72, 95% CI = 1.04-2.84); however, there was no association with fish consumption (RR per 50 g increase per day = 1.22, 95% CI = 0.92-1.62). Our results do not support the conclusion of the World Cancer Research Fund that red or processed meat consumption may possibly increase the risk of pancreatic cancer. The positive association of poultry consumption with pancreatic cancer might be a chance finding as it contradicts most previous findings.

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

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

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

12 Article Dietary intake of iron, heme-iron and magnesium and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort. 2012

Molina-Montes, Esther / Wark, Petra A / Sánchez, María-José / Norat, Teresa / Jakszyn, Paula / Luján-Barroso, Leila / Michaud, Dominique S / Crowe, Francesca / Allen, Naomi / Khaw, Kay-Tee / Wareham, Nicholas / Trichopoulou, Antonia / Adarakis, George / Katarachia, Helen / Skeie, Guri / Henningsen, Maria / Broderstad, Ann Ragnhild / Berrino, Franco / Tumino, Rosario / Palli, Domenico / Mattiello, Amalia / Vineis, Paolo / Amiano, Pilar / Barricarte, Aurelio / Huerta, José-María / Duell, Eric J / Quirós, José-Ramón / Ye, Weimin / Sund, Malin / Lindkvist, Björn / Johansen, Dorthe / Overvad, Kim / Tjønneland, Anne / Roswall, Nina / Li, Kuanrong / Grote, Verena A / Steffen, Annika / Boeing, Heiner / Racine, Antoine / Boutron-Ruault, Marie-Christine / Carbonnel, Franck / Peeters, Petra H M / Siersema, Peter D / Fedirko, Veronika / Jenab, Mazda / Riboli, Elio / Bueno-de-Mesquita, Bas. ·Andalusian School of Public Health. Granada Cancer Registry, Spain. ·Int J Cancer · Pubmed #22438075.

ABSTRACT: Several studies support a protective effect of dietary magnesium against type 2 diabetes, but a harmful effect for iron. As diabetes has been linked to pancreatic cancer, intake of these nutrients may be also associated with this cancer. We examined the association between dietary intake of magnesium, total iron and heme-iron and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In total, 142,203 men and 334,999 women, recruited between 1992 and 2000, were included. After an average follow-up of 11.3 years, 396 men and 469 women developed exocrine pancreatic cancer. Hazard ratios and 95% confidence intervals (CIs) were obtained using Cox regression stratified by age and center, and adjusted for energy intake, smoking status, height, weight, and self-reported diabetes status. Neither intake of magnesium, total iron nor heme-iron was associated with pancreatic cancer risk. In stratified analyses, a borderline inverse association was observed among overweight men (body mass index, ≥ 25 kg/m(2) ) with magnesium (HR(per 100 mg/day increase) = 0.79, 95% CI = 0.63-1.01) although this was less apparent using calibrated intake. In female smokers, a higher intake of heme-iron was associated with a higher pancreatic cancer risk (HR (per 1 mg/day increase) = 1.38, 95% CI = 1.10-1.74). After calibration, this risk increased significantly to 2.5-fold (95% CI = 1.22-5.28). Overall, dietary magnesium, total iron and heme-iron were not associated with pancreatic cancer risk during the follow-up period. Our observation that heme-iron was associated with increased pancreatic cancer risk in female smokers warrants replication in additional study populations.

13 Article Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. 2012

Rohrmann, S / Grote, V A / Becker, S / Rinaldi, S / Tjønneland, A / Roswall, N / Grønbæk, H / Overvad, K / Boutron-Ruault, M C / Clavel-Chapelon, F / Racine, A / Teucher, B / Boeing, H / Drogan, D / Dilis, V / Lagiou, P / Trichopoulou, A / Palli, D / Tagliabue, G / Tumino, R / Vineis, P / Mattiello, A / Rodríguez, L / Duell, E J / Molina-Montes, E / Dorronsoro, M / Huerta, J-M / Ardanaz, E / Jeurnink, S / Peeters, P H M / Lindkvist, B / Johansen, D / Sund, M / Ye, W / Khaw, K-T / Wareham, N J / Allen, N E / Crowe, F L / Fedirko, V / Jenab, M / Michaud, D S / Norat, T / Riboli, E / Bueno-de-Mesquita, H B / Kaaks, R. ·Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Hirschengraben 84, Zürich 8001, Switzerland. sabine.rohrmann@ifspm.uzh.ch ·Br J Cancer · Pubmed #22315049.

ABSTRACT: BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables. RESULTS: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154). CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

14 Article The associations of advanced glycation end products and its soluble receptor with pancreatic cancer risk: a case-control study within the prospective EPIC Cohort. 2012

Grote, Verena A / Nieters, Alexandra / Kaaks, Rudolf / Tjønneland, Anne / Roswall, Nina / Overvad, Kim / Nielsen, Michael R Skjelbo / Clavel-Chapelon, Françoise / Boutron-Ruault, Marie Christine / Racine, Antoine / Teucher, Birgit / Lukanova, Annekatrin / Boeing, Heiner / Drogan, Dagmar / Trichopoulou, Antonia / Trichopoulos, Dimitrios / Lagiou, Pagona / Palli, Domenico / Sieri, Sabina / Tumino, Rosario / Vineis, Paolo / Mattiello, Amalia / Argüelles Suárez, Marcial Vicente / Duell, Eric J / Sánchez, María-José / Dorronsoro, Miren / Huerta Castaño, José María / Barricarte, Aurelio / Jeurnink, Suzanne M / Peeters, Petra H M / Sund, Malin / Ye, Weimin / Regner, Sara / Lindkvist, Björn / Khaw, Kay-Tee / Wareham, Nick / Allen, Naomi E / Crowe, Francesca L / Fedirko, Veronika / Jenab, Mazda / Romaguera, Dora / Siddiq, Afshan / Bueno-de-Mesquita, H Bas / Rohrmann, Sabine. ·Division of Cancer Epidemiology c020, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, Heidelberg, Germany. ·Cancer Epidemiol Biomarkers Prev · Pubmed #22301828.

ABSTRACT: BACKGROUND: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. METHODS: Prediagnostic blood levels of the AGE product Nε-(carboxymethyl)lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). RESULTS: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P(interaction) = 0.002). CONCLUSIONS AND IMPACT: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations.

15 Article Plasma cotinine levels and pancreatic cancer in the EPIC cohort study. 2012

Leenders, Max / Chuang, Shu-Chun / Dahm, Christina C / Overvad, Kim / Ueland, Per Magne / Midttun, Oivind / Vollset, Stein Emil / Tjønneland, Anne / Halkjaer, Jytte / Jenab, Mazda / Clavel-Chapelon, Françoise / Boutron-Ruault, Marie-Christine / Kaaks, Rudolf / Canzian, Federico / Boeing, Heiner / Weikert, Cornelia / Trichopoulou, Antonia / Bamia, Christina / Naska, Androniki / Palli, Domenico / Pala, Valeria / Mattiello, Amalia / Tumino, Rosario / Sacerdote, Carlotta / van Duijnhoven, Fränzel J B / Peeters, Petra H M / van Gils, Carla H / Lund, Eiliv / Rodriguez, Laudina / Duell, Eric J / Pérez, María-José Sánchez / Molina-Montes, Esther / Castaño, José María Huerta / Barricarte, Aurelio / Larrañaga, Nerea / Johansen, Dorthe / Lindkvist, Björn / Sund, Malin / Ye, Weimin / Khaw, Kay-Tee / Wareham, Nicholas J / Michaud, Dominique S / Riboli, Elio / Xun, Wei W / Allen, Naomi E / Crowe, Francesca L / Bueno-de-Mesquita, H Bas / Vineis, Paolo. ·School of Public Health, Imperial College London, London, UK. m.leenders-6@umcutrecht.nl ·Int J Cancer · Pubmed #21953524.

ABSTRACT: Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC cohort), included 146 cases and 146 matched controls. Using liquid chromatography-mass spectrometry, plasma cotinine levels were analyzed on average 8.0 years before cancer onset (5-95% range: 2.8-12.0 years). The relation between plasma cotinine levels and pancreatic cancer was analyzed with conditional logistic regression for different levels of cotinine in a population of never and current smokers. This was also done for the self-reported number of smoked cigarettes per day at baseline. Every increase of 350 nmol/L of plasma cotinine was found to significantly elevate risk of pancreatic cancer [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.11-1.60]. People with a cotinine level over 1187.8 nmol/L, a level comparable to smoking 17 cigarettes per day, have an elevated risk of pancreatic cancer, compared to people with cotinine levels below 55 nmol/L (OR: 3.66, 95% CI: 1.44-9.26). The results for self-reported smoking at baseline also show an increased risk of pancreatic cancer from cigarette smoking based on questionnaire information. People who smoke more than 30 cigarettes per day showed the highest risk compared to never smokers (OR: 4.15, 95% CI: 1.02-16.42). This study is the first to show that plasma cotinine levels are strongly related to pancreatic cancer.

16 Article The association of circulating adiponectin levels with pancreatic cancer risk: a study within the prospective EPIC cohort. 2012

Grote, Verena A / Rohrmann, Sabine / Dossus, Laure / Nieters, Alexandra / Halkjaer, Jytte / Tjønneland, Anne / Overvad, Kim / Stegger, Jakob / Chabbert-Buffet, Nathalie / Boutron-Ruault, Marie-Christine / Clavel-Chapelon, Françoise / Teucher, Birgit / Becker, Susen / Montonen, Jukka / Boeing, Heiner / Trichopoulou, Antonia / Lagiou, Pagona / Trichopoulos, Dimitrios / Palli, Domenico / Sieri, Sabina / Tumino, Rosario / Vineis, Paolo / Mattiello, Amalia / Argüelles, Marcial / Duell, Eric J / Molina-Montes, Esther / Larrañaga, Nerea / Chirlaque, María-Dolores / Gurrea, Aurelio Barricarte / Jeurnink, Suzanne M / Peeters, Petra Hm / Ye, Weimin / Sund, Malin / Lindkvist, Björn / Johansen, Dorthe / Khaw, Kay-Tee / Wareham, Nick / Crowe, Francesca L / Romieu, Isabelle / Rinaldi, Sabina / Jenab, Mazda / Romaguera, Dora / Michaud, Dominique S / Riboli, Elio / Bas Bueno-de-Mesquita, H / Kaaks, Rudolf. ·German Cancer Research Center, Heidelberg, Germany. ·Int J Cancer · Pubmed #21681743.

ABSTRACT: Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a case-control study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.23-0.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.67-3.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development.

17 Article Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. 2011

Grote, V A / Rohrmann, S / Nieters, A / Dossus, L / Tjønneland, A / Halkjær, J / Overvad, K / Fagherazzi, G / Boutron-Ruault, M C / Morois, S / Teucher, B / Becker, S / Sluik, D / Boeing, H / Trichopoulou, A / Lagiou, P / Trichopoulos, D / Palli, D / Pala, V / Tumino, R / Vineis, P / Panico, S / Rodríguez, L / Duell, E J / Molina-Montes, E / Dorronsoro, M / Huerta, J M / Ardanaz, E / Jeurnink, S M / Beulens, J W J / Peeters, P H M / Sund, M / Ye, W / Lindkvist, B / Johansen, D / Khaw, K T / Wareham, N / Allen, N / Crowe, F / Jenab, M / Romieu, I / Michaud, D S / Riboli, E / Romaguera, D / Bueno-de-Mesquita, H B / Kaaks, R. ·Division of Cancer Epidemiology c020, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. ·Diabetologia · Pubmed #21953276.

ABSTRACT: AIMS/HYPOTHESIS: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis. METHODS: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. RESULTS: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥ 6.5%, 48 mmol/mol] vs lowest [≤ 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. CONCLUSIONS/INTERPRETATION: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

18 Article No association between educational level and pancreatic cancer incidence in the European Prospective Investigation into Cancer and Nutrition. 2010

van Boeckel, Petra G A / Boshuizen, Hendriek C / Siersema, Peter D / Vrieling, Alina / Kunst, Anton E / Ye, Weimin / Sund, Malin / Michaud, Dominique S / Gallo, Valentina / Spencer, Elizabeth A / Trichopoulou, Antonia / Benetou, Vasiliki / Orfanos, Philippos / Cirera, Lluis / Duell, Eric J / Rohrmann, Sabine / Hemann, Silke / Masala, Giovanni / Manjer, Jonas / Mattiello, Amalia / Lindkvist, Bjorn / Sánchez, María-José / Pala, Valeria / Peeters, Petra H M / Braaten, Tonje / Tjonneland, Anne / Dalton, Susanne Oksbjerg / Larranaga, Nerea / Dorronsoro, Miren / Overvad, Kim / Illner, Anne-Kathrin / Ardanaz, Eva / Marron, M / Straif, K / Riboli, E / Bueno-de-Mesquita, B. ·National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. p.g.a.vanboeckel@umcutrecht.nl ·Cancer Epidemiol · Pubmed #20829145.

ABSTRACT: INTRODUCTION: Until now, studies examining the relationship between socioeconomic status and pancreatic cancer incidence have been inconclusive. AIM: To prospectively investigate to what extent pancreatic cancer incidence varies according to educational level within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: In the EPIC study, socioeconomic status at baseline was measured using the highest level of education attained. Hazard ratios by educational level and a summary index, the relative indices of inequality (RII), were estimated using Cox regression models stratified by age, gender, and center and adjusted for known risk factors. In addition, we conducted separate analyses by age, gender and geographical region. RESULTS: Within the source population of 407, 944 individuals at baseline, 490 first incident primary pancreatic adenocarcinoma cases were identified in 9 European countries. The crude difference in risk of pancreatic cancer according to level of education was small and not statistically significant (RII=1.14, 95% CI 0.80-1.62). Adjustment for known risk factors reduced the inequality estimates to only a small extent. In addition, no statistically significant associations were observed for age groups (adjusted RII(≤ 60 years)=0.85, 95% CI 0.44-1.64, adjusted RII(>60 years)=1.18, 95% CI 0.73-1.90), gender (adjusted RII(male)=1.20, 95% CI 0.68-2.10, adjusted RII(female)=0.96, 95% CI 0.56-1.62) or geographical region (adjusted RII(Northern Europe)=1.14, 95% CI 0.81-1.61, adjusted RII(Middle Europe)=1.72, 95% CI 0.93-3.19, adjusted RII(Southern Europe)=0.75, 95% CI 0.32-1.80). CONCLUSION: Despite large educational inequalities in many risk factors within the EPIC study, we found no evidence for an association between educational level and the risk of developing pancreatic cancer in this European cohort.

19 Article Metabolic factors and the risk of pancreatic cancer: a prospective analysis of almost 580,000 men and women in the Metabolic Syndrome and Cancer Project. 2010

Johansen, Dorthe / Stocks, Tanja / Jonsson, Håkan / Lindkvist, Björn / Björge, Tone / Concin, Hans / Almquist, Martin / Häggström, Christel / Engeland, Anders / Ulmer, Hanno / Hallmans, Göran / Selmer, Randi / Nagel, Gabriele / Tretli, Steinar / Stattin, Pär / Manjer, Jonas. ·Department of Surgery, Lund University, Malmö, Sweden. dorthe.johansen@med.lu.se ·Cancer Epidemiol Biomarkers Prev · Pubmed #20826833.

ABSTRACT: BACKGROUND: The aim of this study was to investigate the association between factors in metabolic syndrome (MetS; single and combined) and the risk of pancreatic cancer. METHODS: The Metabolic Syndrome and Cancer Project is a pooled cohort containing data on body mass index, blood pressure, and blood levels of glucose, cholesterol, and triglycerides. During follow-up, 862 individuals were diagnosed with pancreatic cancer. Cox proportional hazards analysis was used to calculate relative risks (RR) with 95% confidence intervals using the above-mentioned factors categorized into quintiles and transformed into z-scores. All z-scores were summarized and a second z-transformation creating a composite z-score for MetS was done. All risk estimates were calibrated to correct for a regression dilution bias. RESULTS: The trend over quintiles was positively associated with the risk of pancreatic cancer for mid-blood pressure (mid-BP) and glucose in men and for body mass index, mid-BP, and glucose in women. The z-score for the adjusted mid-BP (RR, 1.10; 1.01-1.20) and the calibrated z-score for glucose (RR, 1.37; 1.14-1.34) were positively associated with pancreatic cancer in men. In women, a positive association was found for calibrated z-scores for mid-BP (RR, 1.34; 1.08-1.66), for the calibrated z-score for glucose (RR, 1.98; 1.41-2.76), and for the composite z-score for MetS (RR, 1.58; 1.34-1.87). CONCLUSION: Our study adds further evidence to a possible link between abnormal glucose metabolism and risk of pancreatic cancer. IMPACT: To our knowledge, this is the first study on MetS and pancreatic cancer using prediagnostic measurements of the examined factors.

20 Article Pre-diagnostic levels of anionic trypsinogen, cationic trypsinogen, and pancreatic secretory trypsin inhibitor in relation to pancreatic cancer risk. 2010

Johansen, Dorthe / Manjer, Jonas / Regner, Sara / Lindkvist, Björn. ·Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden. dorthe.johansen@med.lu.se ·Pancreatology · Pubmed #20484960.

ABSTRACT: BACKGROUND/AIMS: Experimental studies have suggested that trypsinogen may enhance tumor progression and that the ratio between anionic trypsinogen and cationic trypsinogen (HAT/HCT) and between the sum of trypsinogens and pancreatic secretory trypsin inhibitor (PSTI) ((HAT + HCT)/PSTI) are disturbed in patients with pancreatic cancer. The aim of this study was to investigate if pre-diagnostic levels of these parameters are associated with subsequent pancreatic cancer risk. METHODS: A total of 33,346 subjects participated in a health screening programme in Malmö, Sweden. Pancreatic cancer cases (n = 84) were matched to three controls each. HAT, HCT and PSTI were analyzed in pre-diagnostic serum samples. Odds ratios for pancreatic cancer were calculated using logistic regression and were then stratified for other risk factors. RESULTS: In the main analysis, a statistically significant association between the ratio between HAT/HCT and pancreatic cancer was observed for all, for the crude OR and for the ORs adjusted for sex, BMI or Helicobacter pylori. When stratified for sex, statistically significant associations were found for females in the crude OR and for the ORs adjusted for time to analysis, BMI, alcohol consumption or H. pylori. There was a positive association between the ratio of HAT/HCT to pancreatic cancer in the intermediate/high alcohol consumption group and subjects with a BMI <25. The sum of trypsinogens showed a similar pattern, but was only of borderline significance in the intermediate/high alcohol consumption group. CONCLUSION: Our hypothesis predicted an increased risk for pancreatic cancer related to an imbalance between trypsin activity and trypsin inhibition capacity. The findings concerning the ratio of HAT/HCT are in line with this. The results related to analyses stratified for other risk factors should be considered as mainly explorative.