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

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

Research output: Contribution to journalArticle

41 Citations (Scopus)

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, 6.92, 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 0.76, 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. (c) 2008 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)2170-2179
Number of pages10
JournalInternational Journal of Cancer
Volume123
Issue number9
Early online date15 Aug 2008
DOIs
Publication statusPublished - 1 Nov 2008

Keywords

  • colorectal neoplasms
  • case-control studies
  • single nucleotide polymorphism
  • vitamin D
  • vitamin D receptor
  • receptor gene polymorphisms
  • colon-cancer
  • rectal-cancer
  • dairy-products
  • United-States
  • prospective cohort
  • D metabolites
  • Finnish men
  • calcium
  • women

Cite this

Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI 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.

In: International Journal of Cancer, Vol. 123, No. 9, 01.11.2008, p. 2170-2179.

Research output: Contribution to journalArticle

Theodoratou, Evropi ; Farrington, Susan M. ; Tenesa, Albert ; McNeill, Geraldine ; Cetnarskyj, Roseanne ; Barnetson, Rebecca A. ; Porteous, Mary E. ; Dunlop, Malcolm G. ; Campbell, Harry. / Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding. In: International Journal of Cancer. 2008 ; Vol. 123, No. 9. pp. 2170-2179.
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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, 6.92, 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 0.76, 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. (c) 2008 Wiley-Liss, Inc.",
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T1 - Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding

AU - Theodoratou, Evropi

AU - Farrington, Susan M.

AU - Tenesa, Albert

AU - McNeill, Geraldine

AU - Cetnarskyj, Roseanne

AU - Barnetson, Rebecca A.

AU - Porteous, Mary E.

AU - Dunlop, Malcolm G.

AU - Campbell, Harry

PY - 2008/11/1

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N2 - 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, 6.92, 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 0.76, 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. (c) 2008 Wiley-Liss, Inc.

AB - 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, 6.92, 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 0.76, 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. (c) 2008 Wiley-Liss, Inc.

KW - colorectal neoplasms

KW - case-control studies

KW - single nucleotide polymorphism

KW - vitamin D

KW - vitamin D receptor

KW - receptor gene polymorphisms

KW - colon-cancer

KW - rectal-cancer

KW - dairy-products

KW - United-States

KW - prospective cohort

KW - D metabolites

KW - Finnish men

KW - calcium

KW - women

U2 - 10.1002/ijc.23769

DO - 10.1002/ijc.23769

M3 - Article

VL - 123

SP - 2170

EP - 2179

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 9

ER -