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Int J Cancer. 2015 Dec 15;137(12):2904-14. doi: 10.1002/ijc.29669. Epub 2015 Jul 16.

Body iron status and gastric cancer risk in the EURGAST study.

Author information

1
Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L'Hospitalet De Llobregat, Barcelona, Spain.
2
IISPV, Departament De Ciències Mèdiques Bàsiques, Universitat Rovira I Virgili (URV), Tarragona, Spain.
3
Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.
4
Escuela Andaluza De Salud Pública, Instituto De Investigación Biosanitaria Ibs.GRANADA, Hospitales Universitarios De Granada/Universidad De Granada, Granada, Spain.
5
CIBER De Epidemiología Y Salud Pública (CIBERESP), Madrid, Spain.
6
Department of Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
7
Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
8
Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom.
9
Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
10
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, the Arctic University of Norway, Tromsø, Norway.
11
Department of Research, Cancer Registry of Norway, Oslo, Norway.
12
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
13
Samfundet Folkhälsan, Helsinki, Finland.
14
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, Italy.
15
Dipartamento Di Medicina Clinica E Chirugia, Federico II University, Naples, Italy.
16
Cancer Registry and Histopathology Unit, "Civic - M.P.Arezzo" Hospital, ASP Ragusa, Italy.
17
Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy.
18
Molecular and Genetic Epidemiology Unit, HuGeF - Human Genetics Foundation - Torino, Torino, Italy.
19
Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital Malmo, Lund University, Malmo, Sweden.
20
Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women's Health Team, Villejuif, France.
21
Université Paris Sud, UMRS 1018, Villejuif, France.
22
Institut Gustave Roussy, Villejuif, France.
23
Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
24
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
25
Danish Cancer Society Research Center, Copenhagen, Denmark.
26
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
27
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
28
Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
29
Department of Epidemiology, Regional Health Council, Murcia, Spain.
30
IMIB-Arrixaca, Murcia, Spain.
31
Basque Regional Health Department, Public Health Direction and Biodonostia-Ciberesp, San Sebastian, Spain.
32
Public Health Directorate, Asturias, Spain.
33
Navarre Public Health Institute, Pamplona, Spain.
34
International Agency for Research on Cancer (IARC-WHO), Lyon, France.
35
WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece.
36
Hellenic Health Foundation, Athens, Greece.

Abstract

Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) 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 prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2  = 0.80, 95% CI = 0.72-0.88; OR10%increment  = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 µg/dl  = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.

KEYWORDS:

gastric cancer; iron homeostasis; nested case-control study

PMID:
26135329
PMCID:
PMC6284801
DOI:
10.1002/ijc.29669
[Indexed for MEDLINE]
Free PMC Article

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