Author(s):
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Crusius, J.B.; Canzian, F.; Capella, G.; Pena, A.S.; Pera, G.; Sala, N.; Agudo, A.; Rico, F.; Giudice, G. Del; Palli, D.; Plebani, M.; Boeing, H.; Bueno-De-Mesquita, H.B.; Carneiro, F.; Pala, V.; Save, V.E.; Vineis, P.; Tumino, R.; Panico, S.; Berglund, G.; Manjer, J.; Stenling, R.; Hallmans, G.; Martinez, C.; Dorronsoro, M.; Barricarte, A.; Navarro, C; Quiros, J.R.; Allen, N.; Key, T.J.; Binghan, S.; Caldas, C.; Linseisen, J.; Kaaks, R.; Overvad, K.; Tjonneland, A.;
Buchner, F.L.
; Peeters, P.H.M.; Numans, M.E.; Clavel-Chapelon, F.; Trichopoulou, A.; Lund, E.; Jenab, M.; Rinaldi, S.; Ferrari, P.; Riboli, E.; Gonzalez, C.A.
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Subject:
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UMCN 1.2: Molecular diagnosis, prognosis and monitoring |
Abstract:
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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.
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