JBA Crusius, F Canzian, G Capellá, AS Peña, G Pera, N Sala, A Agudo, F Rico, G Del Giudice, D Palli, M Plebani, H Boeing, HB Bueno-de-Mesquita, F Carneiro, V Pala, VE Save, P Vineis, R Tumino, S Panico, G Berglund, J Manjer, R Stenling, G Hallmans, C Martínez, M Dorronsoro, A Barricarte, C Navarro, JR Quirós, N Allen, TJ Key, S Binghan, C Caldas, J Linseisen, R Kaaks, K Overvad, A Tjønneland, FC Büchner, PHM Peeters, ME Numans, F Clavel-Chapelon, A Trichopoulou, E Lund, M Jenab, S Rinaldi, P Ferrari, E Riboli, CA González
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 alpha 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.