"This project aims to investigate the role of vitamin D status in survival of patients diagnosed with oesophageal or gastric cancer. The ultimate goal of the project is to help inform cancer treatment and improve survival in these patients.Both oesophageal and gastric cancer have exceptionally poor prognosis, with a 5-year survival of only 15-20%. Moreover, little improvement in survival has been made in either cancer type. Observational and ecological studies have investigated associations between vitamin D proxies (e.g. vitamin D dietary intake, sunshine hours or UVB irradiance) and upper gastrointestinal cancers. These studies largely show poorer prognosis in cancer patients with lower estimated vitamin D levels. Vitamin D deficiency is prevalent in Europe and the investigation of any potential detrimental effects of vitamin D deficiency is of major significance for the population.To date, no well-designed study has investigated the relationship between post-diagnostic circulating 25-hydroxyvitamin D (25-OHD, the best indicator of vitamin D status) and prognosis in oesophageal cancer patients. Therefore, the main aim of this proposal is to explore the relationship between 25-OHD concentration at the time of diagnosis and survival in oesophageal cancer patients. We also propose to investigate, for the first time in Caucasians, the relationship between 25-OHD and survival in gastric cancer patients.Furthermore, we seek to assess the mechanism of these associations, as understanding the biological pathway could add evidence in support of their causality. The principle way that vitamin D exerts its biological action is by binding to the vitamin D receptor (VDR). Therefore, presence of functioning VDR is crucial for its downstream effects, such as expression of E-cadherin (CDH1). To address this, we will assess the expression of the VDR and CDH1 genes in tissue, and we will genotype common polymorphisms in VDR gene that are known to affect its function."