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Hepcidin levels and gastric cancer risk in the EPIC-EurGast study.

Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L'Hospitalet De Llobregat, Barcelona, Spain. Department of Nursing of Public Health, Mental Health and Maternity and Child Health School of Nursing Universitat de Barcelona,Spain. Nutrition and Public Health Unit, Faculty of Medicine and Health Sciences, Research Group in Nutrition and Mental Health (NUTRISAM), Institut d'investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), Reus, Tarragona, Spain. Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, United Kingdom. Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Foundation under Public Law, Heidelberg, Germany. Department of Clinical Sciences, Lund University, Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden. Department of Internal Medicine, Lund University, Skane University Hospital, Malmö, Sweden. Cancer Registry and Histopathology Unit, "Civic - M.P. Arezzo" hospital, ASP Ragusa, Italy. Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO Florence, Italy. Unit of Epidemiology, Regional Health Service, Grugliasco, Turin, Italy. Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. Department of Clinical and Experimental Medicine, Federico II University Naples, Italy. Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France. Cancer Epidemiology Unit; Nuffield Department of Population Health, University of Oxford, United Kingdom. Department Public Health and Primary Care, University of Cambridge, United Kingdom. Danish Cancer Society Research Center, Copenhagen, Denmark. Department of Public Health, Section for Epidemiology, Aarhus University, Denmark. 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, Greece. Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs, Granada, Hospitales Universitarios de Granada/Universidad de Granada, Spain. CIBER de Epidemiología y Salud Pública (CIBERESP), Spain. Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. Basque Regional Health Department, San Sebastian, Spain. Navarre Public Health Institute, Pamplona, Spain. Public Health Directorate, Asturias, Spain. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom.

International journal of cancer. 2017;(5):945-951
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Abstract

Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93-0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: -69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.

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Publication Type : Multicenter Study

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MeSH terms : Hepcidins