Investigation of gene–environment interactions between vitamin D and colorectal cancer susceptibility genetic variants in large bowel epithelium

• Published in: The Lancet (British edition) 2016-02, Vol.387, p.S102-S102
• Main Authors: Vaughan-Shaw, Peter G, MBChB, Grimes, Graeme, MRes, Ochocka, Anna-Maria, PhD, Dunbar, Karen, BVMS, Timofeeva, Maria, PhD, Din, Fahrat V N, MD, Farrington, Susan M, PhD, Dunlop, Malcolm G, Prof
• Format: Article
• Language: English
• Subjects: Colorectal carcinoma; Genetic variance; Genotype-environment interactions; Internal Medicine; Medical research; Vitamin D
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(16)00489-X

Abstract Background Observational data implicate vitamin D deficiency in the aetiology of colorectal cancer, yet causality is not established. In-house epidemiological data suggest that the colorectal cancer susceptibility locus rs9929218 might interact with vitamin D concentration to impact risk. This single nucleotide polymorphism is also intronic within CDH1 , a tumour suppressor gene. This study aimed to determine whether vitamin D impacts on expression of CDH1 and interacts with common genetic variance linked to colorectal cancer susceptibility. Methods Ten cell lines were treated with calcitriol (50 nM) for 16 h and induction of CDH1 assessed with real-time PCR. Colorectal epithelial organoids (three mouse, three human) were cultured and the effect of calcitriol (0·5–100 nM, 16–24 h) investigated. Samples from normal colorectal mucosa were taken from 110 study participants, and the association between vitamin D concentration and rs9929218 genotype with gene expression assessed (HT12 microarray). A subgroup underwent vitamin D supplementation (3200 IU orally) and repeat sampling at 6 and 12 weeks. Findings Calcitriol treatment increased CDH1 expression in five cell lines (1·3–2·8-fold, p