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Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a Fok I variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding
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 Scotti...
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Published in: | International journal of cancer 2008-11, Vol.123 (9), p.2170-2179 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. © 2008 Wiley‐Liss, Inc. |
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ISSN: | 0020-7136 1097-0215 |
DOI: | 10.1002/ijc.23769 |