Approved research

Investigation of the association between the main vitamin D predictors and vitamin D status, and the role of vitamin D in survival of patients diagnosed with oesophageal or gastric cancer

Lay summary

First, we will investigate the association between circulating vitamin D concentration (25-hydroxyvitamin D) and vitamin D status proxies: (i) UVB exposure, (ii) supplement use, (iii) diet and (iv) genetic variation in vitamin D metabolisms genes. Many studies report reduced cancer risk and mortality associated with higher levels of vitamin D. However, there is still controversy in relation to rarer cancers. Therefore, we next aim to examine an association between oesophageal and gastric cancer survival and: 25-hydroxyvitamin D, and also with vitamin D proxies (UVB exposure, supplements use and genetic variation in vitamin D metabolisms genes). We will clarify the relationship between vitamin D proxies and 25-hydroxyvitamin D concentration. This is important as it will inform on the suitability of using those proxies in research, for example when 25(OH)D is not available. Very few studies examined the role of vitamin D in oesophageal and gastric cancer survival, although those cancer sites have among the worst prognoses of all cancers. Should significant association be found, this could be of great importance, especially since vitamin D deficiency has been found to be highly prevalent in populations residing at high latitudes, such as UK and Ireland. We will examine the correlation between 25(OH)D concentration and vitamin D proxies (UVB, supplement/dietary intake and genetic polymorphisms). We will use Kaplan-Meier analysis to show unadjusted survival difference according to vitamin D, and Cox portional hazard regression models to investigate the associations between vitamin D (25(OH)D and proxies) and survival in upper gastrointestinal cancers. Models will be adjusted for other relevant factors (eg. age, gender, cancer site) and known confounders, such as smoking, alcohol or BMI. The ultimate goal of the project is to help inform cancer treatment and improve survival in these patients. We request to obtain selected data for the full UK Biobank cohort. For the first research question, we will explore correlations between 25(OH)D and vitamin D proxies (UVB, supplement/dietary intake and genetic polymorphisms), in the full cohort. For the second research question, we will focus on all participants in UK Biobank with prevalent or incident oesophageal and gastric cancer (estimated at ~800 incident and prevalent upper gastrointestinal cases) and use age and gender matched cancer-free controls (case:control ratio of 1:10, ie. ~8,000 controls).