Background: Dietary and lifestyle factors and infection with the bacterium Helicobacter pylori (H. pylori) play an important role in gastric cancer (GC) aetiology. Mechanisms of oxidative and inflammatory stresses are important for GC initiation and progression. The micronutrient Selenium (Se) exerts anti-oxidant, anti-inflammatory (and proposed anti-tumourigenic) effects through selenoproteins Thus, it is plausible that suboptimal intakes of Se and variations in selenoprotein genes may contribute to GC development. We hypothesise that the contribution of Se levels to GC risk is most relevant for populations, like in Ireland and many in Europe, where Se intake is relatively low and to individuals of particular selenoprotein genotypes.
Objectives: Given a strong rationale but inadequate human data from prospective studies, we will investigate if GC risk is associated with pre-diagnostic Se status and candidate selenoprotein gene variants, stratified by important potential effect dietary/lifestyle factors modifiers, particularly H. pylori status, sex, alcohol, smoking, obesity, and weight changes.
Methods: We will measure in 750 cases and 750 matched controls nested within the European-Prospective-Investigation-of-Cancer-and-Nutrition (EPIC) cohort the circulating levels of Se and major selenoproteins (Selenoprotein P, SePP and Glutathione peroxidase 3, GPx3) and assess their association with GC risk. Additionally, candidate selenoprotein gene variants will be genotyped in DNA available from these case-control pairs and tested for association with altered GC susceptibility risk, individually and in interaction with the Se status biomarkers. Conditional logistic regression will be used to assess the associations with GC risk together with pathway-based SNP_Se analyses and other biologically plausible interactions (e.g., smoking, alcohol, sex, BMI, H. pylori status, and tumour type).
Impact: This study will provide evidence of Se status biomarkers (in combination with genetic background and lifestyle factors) as potential GC risk indicators and may allow identifying sub-group populations who could benefit from increased dietary Se for GC prevention.
