Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by aFokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding

Theodoratou, Evropi; Farrington, Susan M; Tenesa, Albert; McNeill, Geraldine; Cetnarskyj, Roseanne; Barnetson, Rebecca A; Porteous, Mary E; Dunlop, Malcolm G; Campbell, Harry

Abstract

Vitamin D has anticarcinogenic properties and might influence colorectal cancer (CRC) risk, but the epidemiological evidence is inconsistent. Many mechanisms of action for vitamin D have been proposed, with some of them initiating via its binding to the vitamin D receptor (VDR). Using a large Scottish case–control study, we investigated (i) main associations between CRC, vitamin D and calcium dietary intake and 4 VDR single nucleotide polymorphisms (rs10735810, rs1544410, rs11568820, rs7975232) and (ii) interaction associations between the VDR variants, vitamin D and calcium intakes. Inverse and dose-dependent associations were found between CRC risk, dietary [Odds ratio (OR) = 0.77, 95% confidence intervals (CI) 0.63, 0.92, p-trend = 0.012] and total vitamin D (OR = 0.80, 95% CI 0.65, 0.98, p-trend = 0.014) intake in multivariable-adjusted logistic regression models, whereas neither calcium intake nor any of the VDR variants were associated with CRC. Additionally, we observed statistically significant interactions (case–control, case-only designs) between vitamin D and calcium intake and rs10735810 (p-interaction 0.02, 0.006, respectively). We conducted meta-analyses of cohort, case–control and serum studies that also showed an inverse association between dietary vitamin D intake and CRC (serum studies: combined OR = 0.70, 95% CI 0.56, 0.87). The evidence of interaction we report here further supports the inverse association between vitamin D mediated through binding to the VDR.

Citation

Theodoratou, E., Farrington, S. M., Tenesa, A., McNeill, G., Cetnarskyj, R., Barnetson, R. A., …Campbell, H. (2008). Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by aFokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding. International Journal of Cancer, 123, 2170-2179. https://doi.org/10.1002/ijc.23769

• Journal Article Type: Article
• Publication Date: 2008
• Deposit Date: Mar 13, 2014
• Print ISSN: 0020-7136
• Electronic ISSN: 1097-0215
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 123
• Pages: 2170-2179
• DOI: https://doi.org/10.1002/ijc.23769
• Keywords: colorectal neoplasms; case–control studies; single nucleotide polymorphism; vitamin D; vitamin D receptor
• Public URL: http://researchrepository.napier.ac.uk/id/eprint/6618
• Publisher URL: http://dx.doi.org/10.1002/ijc.23769