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CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

2008; Elsevier BV; Volume: 44; Issue: 6 Linguagem: Inglês

10.1016/j.ejca.2008.02.003

1879-0852

Mazda Jenab, James McKay, Pietro Ferrari, Carine Biessy, Stewart Laing, Gabriel Maria Capella Munar, Núria Sala, Salvador Peña, J. Bart A. Crusius, Kim Overvad, Majken K. Jensen, Anja Olsen, Anne Tjønneland, Françoise Clavel‐Chapelon, Marie‐Christine Boutron‐Ruault, Rudolf Kaaks, Jakob Linseisen, Heiner Boeing, Manuela M. Bergmann, Antonia Trichopoulou, Christina Georgila, Θεοδώρα Ψαλτοπούλου, Amalia Mattiello, Paolo Vineis, Valeria Pala, Domenico Palli, ­Rosario ­Tumino, Mattijs E. Numans, Petra H. Peeters, H. Bas Bueno-de-Mesquita, Eiliv Lund, Eva Ardanáz, María‐José Sánchez, Miren Dorronsoro, Carmen Navarro, J. Ramón Quirós, Göran Hallmans, Roger Stenling, Jonas Manjer, Sara Regnér, Tim Key, Sheila Bingham, Kay‐Tee Khaw, Nadia Slimani, Sabina Rinaldi, Paolo Boffetta, Fátima Carneiro, Elio Ríboli, Carlos A. González,

Cancer-related gene regulation

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in GC. Germline mutations in the E-Cadherin gene (CDH1) have been identified in hereditary diffuse GC. Also, a promoter polymorphism at position −160 C/A has been suggested to lead to transcriptional down regulation and has been shown to affect GC risk in some studies. However, very little information exists on the GC risk association of other CDH1 polymorphisms and it is unclear whether any associations may be different by GC anatomical sites or histological types. Thus, a case–control study (cases = 245/controls = 950) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted to assess the GC risk association of eight CDH1 gene polymorphisms. None of the CDH1 polymorphisms or haplotypes analysed were associated with GC risk and no differences of effect were observed by Helicobacter pylori infection status. However, three CDH1 polymorphisms in the same haplotype block, including the CDH1−160C/A, interacted with smoking to increase GC risk in smokers but not in never smokers. These findings should be confirmed in larger independent studies.