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Dietary folate intake and pancreatic cancer risk: Results from the European prospective investigation into cancer and nutrition
Authors:Jin Young Park  H. Bas Bueno-de-Mesquita  Pietro Ferrari  Elisabete Weiderpass  Jordi de Batlle  Anne Tjønneland  Cecilie Kyro  Vinciane Rebours  Marie-Christine Boutron-Ruault  Francesca Romana Mancini  Verena Katzke  Tilman Kühn  Heiner Boeing  Antonia Trichopoulou  Carlo La Vecchia  Maria Kritikou  Giovanna Masala  Valeria Pala  Rosario Tumino  Salvatore Panico  Petra H. Peeters  Guri Skeie  Susana Merino  Eric J. Duell  Miguel Rodríguez-Barranco  Miren Dorronsoro  Maria-Dolores Chirlaque  Eva Ardanaz  Björn Gylling  Jörn Schneede  Ulrika Ericson  Hanna Sternby  Kay-Tee Khaw  Kathryn E. Bradbury  Inge Huybrechts  Dagfinn Aune  Paolo Vineis  Nadia Slimani
Affiliation:1. International Agency for Research on Cancer, Lyon, France;2. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands

Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands

School of Public Health, Imperial College London, London, United Kingdom;3. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland;4. Group of Translational Research in Respiratory Medicine, IRBLleida, Hospital Universitari Arnau de Vilanova and Santa Maria, Lleida, Spain

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain;5. Danish Cancer Society Research Center, Copenhagen, Denmark;6. Pancreatology Unit, Beaujon Hospital, Clichy, France

INSERM—UMR 1149, University Paris 7, France;7. CESP, INSERM U1018, University of Paris-Sud, UVSQ, Université Paris-Saclay, France

Gustave Roussy, Villejuif, France;8. German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany;9. Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Germany;10. Hellenic Health Foundation, Athens, Greece;11. Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network—ISPRO, Florence, Italy;12. Epidemiology and Prevention Unit, IRCCS Foundation National Cancer Institute, Milan, Italy;13. Cancer Registry and Histopathology Department, ‘Civic—M.P. Arezzo’ Hospital, ASP Ragusa, Italy;14. Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy;15. School of Public Health, Imperial College London, London, United Kingdom

Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht;16. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway;17. Public Health Directorate, Asturias, Spain;18. Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain;19. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain

CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain;20. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Dirección de Salud Pública y Adicciones, Gobierno Vasco, Vitoria, Spain

Instituto de Investigación Sanitaria Biodonostia, San Sebastián, Spain;21. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain

Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain;22. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

Navarra Public Health Institute, Pamplona, Spain

IdiSNA, Navarra Institute for Health Research, Pamplona, Spain;23. Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden;24. Department of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden;25. Diabetes and Cardiovascular disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Sweden;26. Department of Surgery, Institution of Clinical Sciences Malmö, Lund University, Sweden;27. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom;28. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom;29. School of Public Health, Imperial College London, London, United Kingdom

Bjørknes University College, Oslo, Norway;30. School of Public Health, Imperial College London, London, United Kingdom

IIGM Foundation, Turin, Italy

Abstract:
Pancreatic cancer (PC) has an exceptionally low survival rate and primary prevention strategies are limited. Folate plays an important role in one-carbon metabolism and has been associated with the risk of several cancers, but not consistently with PC risk. We aimed to investigate the association between dietary folate intake and PC risk, using the standardised folate database across 10 European countries. A total of 477,206 participants were followed up for 11 years, during which 865 incident primary PC cases were recorded. Folate intake was energy-adjusted using the residual method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. In multivariable analyses stratified by age, sex, study centre and adjusted for energy intake, smoking status, BMI, educational level, diabetes status, supplement use and dietary fibre intake, we found no significant association between folate intake and PC risk: the HR of PC risk for those in the highest quartile of folate intake (≥353 μg/day) compared to the lowest (<241 μg/day) was 0.81 (95% CI: 0.51, 1.31; ptrend = 0.38). In current smokers, a positive trend was observed in PC risk across folate quartiles [HR = 4.42 (95% CI: 1.05, 18.62) for ≥353 μg/day vs. <241 μg/day, ptrend = 0.01]. Nonetheless, there was no significant interaction between smoking and dietary folate intake (pinteraction = 0.99). We found no association between dietary folate intake and PC risk in this large European study.
Keywords:dietary folate intake  pancreatic cancer  EPIC study
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