Scottish Colorectal Cancer Vitamin D Intervention Study (SCoViDS) [RNA-seq]

Controversy surrounds whether vitamin D reduces colorectal cancer (CRC) risk, and/or beneficially impacts on CRC survival. We sought to delineate the transcriptomic in vivo response of human colorectal epithelium to vitamin D supplementation, define inter-subject variability and develop a predictive biomarker of response consistent with anti-tumour effects. Methodology Blood and rectal normal mucosa (NM) were sampled (176 subjects) and correlation sought between circulating vitamin D (25-OHD) level and NM gene expression (HT12 microarray) in the observational study. Oral vitamin D (3200IU/day) supplements were administered to 50 participants in an intervention study. Blood and NM (sigmoidoscopic biopsy) were sampled after 12 weeks. Transcriptomic analysis (HT12 and RNAseq) of post-treatment biopsies assessed enrichment for candidate genes and GO processes prioritised in the observational study. We identified transcriptomic changes in rectum that are consistent with anti-tumour responses. We then sought blood biomarkers predicting this response using receiver-operator curves and calculation of C-statistic. An independent expression dataset (BEST-D trial) was then used to validate candidate blood biomarkers of vitamin D response. 98 rectal biopsy from 49 Patient's taken pre and post (12 weeks) oral vitamin D supplementation