Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence

✍ Scribed by Richard A. Hubner; Kenneth R. Muir; Jo-Fen Liu; Richard F.A. Logan; Matthew J. Grainge; Richard S. Houlston;; Members of the UKCAP Consortium

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 114 KB
• Volume: 123
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23536

✦ Synopsis

Abstract

Vitamin D receptor (VDR) activation inhibits proliferation and angiogenesis in the colorectal epithelium, and inhibits metastasis of colorectal tumors. Polymorphisms in the VDR gene alter receptor cellular levels and functioning, and may confer altered susceptibility to colorectal neoplasia. We aimed to investigate the influence of VDR polymorphisms and dietary factors impacting on vitamin D metabolism on colorectal adenoma (CRA) recurrence. Data on dietary intakes of calcium, vitamin D and dairy products were collected from 853 participants in the United Kingdom Colorectal Adenoma Prevention trial, a randomized trial of aspirin and folate for CRA recurrence prevention. The VDR Cdx2, __Fok__I, __Bsm__I, __Apa__I and __Taq__I polymorphisms were genotyped in 546 participants with available DNA, and gene–diet interaction analyses performed in 480. Dairy product intake was inversely related to CRA recurrence risk independent of calcium and vitamin D [relative risk (RR) = 0.64; 95% confidence intervals (CIs): 0.47–0.88, for subjects in the highest compared to lowest intake tertile, p~trend~ = 0.005]. Milk accounted for 60% of dairy product intake, and on analysis of milk and nonmilk dairy products separately recurrence risk in individuals in the highest tertile of milk intake was half that of lowest tertile individuals (RR = 0.52; 95% CI: 0.38–0.72, p~trend~ = 3.2 × 10^−5^), whereas nonmilk dairy products did not influence recurrence. VDR polymorphism genotypes and haplotypes did not directly alter recurrence risk, but the reduction in risk associated with high dairy product intake was confined to individuals with __Apa__I aA/AA genotype (p~interaction~ = 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence. © 2008 Wiley‐Liss, Inc.