Annals of Oncology Advance Access originally published online on July 14, 2008
Annals of Oncology 2008 19(11):1894-1902; doi:10.1093/annonc/mdn400
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gastrointestinal tumors |
Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST)
1 Laboratory of Immunogenetics, Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
2 International Agency for Research on Cancer, Lyon, France
3 Translational Research Laboratory
4 Department of Epidemiology, IDIBELL—Catalan Institute of Oncology, Barcelona
5 Center for Molecular and Medical Genetics, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)—Institut de Recerca Oncològica, Barcelona, Spain
6 Immunobiological Research Institute of Siena (IRIS) Research Center, Chiron-Vaccines, Siena
7 Molecular and Nutritional Epidemiology Unit, Centro per lo Studio e la Prevenzione Oncologica, Scientific Institute of Tuscany, Florence
8 Department of Laboratory Medicine, Azienda Ospedaliera—Università di Padova, Padova, Italy
9 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany
10 Center for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
11 Institute of Pathology and Molecular Immunology of the University of Porto and Medical Faculty/H.S. Joao, Porto, Portugal
12 Epidemiology Unit, National Cancer Institute, Milan, Italy
13 Pathology Department, Addenbrooke's Hospital, Cambridge, UK
14 Department of Epidemiology and Public Health, Imperial College London, London, UK
15 Department of Biomedical Science, University of Torino, Turin
16 Cancer Registry Azienda Ospedaliera Civile-M.P. Arezzo, Ragusa
17 Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy
18 Department of Medicine, Lund University Malmö, Malmö
19 Department of Surgery, University Hospital, Malmö
20 Department of Medical Biosciences, Pathology
21 Department of Nutritional Research, Umeå University, Sweden
22 Andalusian School of Public Health, Granada
23 Department of Public Health of Guipuzkoa, San Sebastian
24 Public Health Institute, Navarra
25 Department of Epidemiology, Health Council of Murcia
26 Public Health and Health Planning Directorate, Asturias, Spain (Dirección General de Salud Pública, Consejería de Salud y Servicios Sanitarios Asturias, Spain)
27 Cancer Research UK, Epidemiology Unit, University of Oxford, Oxford
28 Medical Research Council Dunn Human Nutrition Unit, Cambridge
29 Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Center, Cambridge, UK
30 Division of Clinical Epidemiology, German Cancer Research Center, Heidelberg, Germany
31 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg
32 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
33 Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
34 INSERM, U 521, Institut Gustave Roussy, Villejuif, France
35 Department of Hygiene and Epidemiology, Medical School University of Athens, Athens, Greece
36 Institute of Community Medicine, University of Tromso, Tromso, Norway
* Correspondence to: G. Capellá, Translational Research Laboratory, Catalan Institute of Oncology, Barcelona, Spain. Tel: +34-93-260-7952; Fax: +34-93-260-7466; E-mail: gcapella{at}iconcologia.net
Background: The relative contribution to gastric cancer (GC) risk of variants in genes that determine the inflammatory response remains mostly unknown and results from genotyping studies are inconsistent.
Patients and methods: A nested case–control study within the prospective European Prospective Investigation into Cancer and Nutrition cohort was carried out, including 248 gastric adenocarcinomas and 770 matched controls. Twenty common polymorphisms at cytokine genes [interleukin (IL)1A, IL1B, IL1RN, IL4, IL4R, IL6, IL8, IL10, IL12A, IL12B, lymphotoxin 
and tumor necrosis factor (TNF)] were analyzed. Antibodies against Helicobacter pylori (Hp) and CagA were measured.
Results: IL1RN 2R/2R genotype [odds ratio (OR) 2.43; 95% confidence interval (CI) 1.19–4.96] and allele IL1RN Ex5–35C were associated with an increased risk of Hp(+) non-cardia GC. IL8 –251AA genotype was associated with a decreased risk of Hp(+) non-cardia GC (OR 0.51; 95% CI 0.32–0.81), mainly of the intestinal type. These associations were not modified by CagA status. Carriers of IL1B –580C and TNF –487A alleles did not associate with an increased risk. A moderately increased risk of Hp(+) non-cardia GC for IL4R –29429T variant was observed (OR 1.74; 95% CI 1.15–2.63).
Conclusion: This prospective study confirms the association of IL1RN polymorphisms with the risk of non-cardia GC and indicates that IL8 –251T>A may modify the risk for GC.
Key words: cytokine genes, gastric carcinoma, polymorphisms, severe chronic atrophic gastritis
Present address: Genomic Epidemiology Group, Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany Received for publication January 17, 2008. Revision received May 23, 2008. Accepted for publication May 26, 2008.