|Title||Cytokine gene polymorphisms and the risk of adenocarcinoma of the stomach in the European prospective investigation into cancer and nutrition (EPIC-EURGAST).|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Crusius, JBA, Canzian, F, Capellá, G, Peña, AS, Pera, G, Sala, N, Agudo, A, Rico, F, Del Giudice, G, Palli, D, Plebani, M, Boeing, H, Bueno-de-Mesquita, HB, Carneiro, F, Pala, V, Save, VE, Vineis, P, Tumino, R, Panico, S, Berglund, G, Manjer, J, Stenling, R, Hallmans, G, Martinez, C, Dorronsoro, M, Barricarte, A, Navarro, C, Quiros, JR, Allen, N, Key, TJ, Binghan, S, Caldas, C, Linseisen, J, Kaaks, R, Overvad, K, Tjønneland, A, Büchner, FC, Peeters, PHM, Numans, ME, Clavel-Chapelon, F, Trichopoulou, A, Lund, E, Jenab, M, Rinaldi, S, Ferrari, P, Riboli, E, González, CA|
|Date Published||2008 Nov|
|Keywords||Adenocarcinoma, Adult, Aged, Case-Control Studies, Cytokines, Europe, Female, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Interleukins, Lymphotoxin-alpha, Male, Middle Aged, Nutritional Status, Polymorphism, Genetic, Prospective Studies, Stomach Neoplasms, Tumor Necrosis Factor-alpha|
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.
|Alternate Journal||Ann. Oncol.|
|Grant List|| / / British Heart Foundation / United Kingdom |
/ / Cancer Research UK / United Kingdom
/ / Department of Health / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom