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.
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.
Theodoratou
Evropi
E
Public Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom.
Farrington
Susan M
SM
Tenesa
Albert
A
McNeill
Geraldine
G
Cetnarskyj
Roseanne
R
Barnetson
Rebecca A
RA
Porteous
Mary E
ME
Dunlop
Malcolm G
MG
Campbell
Harry
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D002136:Calcium, Dietary / Q000008:administration & dosage; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000209:etiology / Q000517:prevention & control*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D014807:Vitamin D / Q000008:administration & dosage* / Q000378:metabolism
D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D014807:Vitamin D; C035042:endodeoxyribonuclease FokI; D015252:Deoxyribonucleases, Type II Site-Specific