Genetic variation in the vitamin D receptor (VDR) and the vitamin D-binding protein (GC) and risk for colorectal cancer: results from the Colon Cancer Family Registry.
Epidemiologic evidence supports a role for vitamin D in colorectal cancer (CRC) risk. Variants in vitamin D-related genes might modify the association between vitamin D levels and CRC risk. In this analysis, we did a comprehensive evaluation of common variants in the vitamin D receptor (VDR) and the vitamin D-binding protein (GC; group-specific component) genes using a population-based case-unaffected sibling control design that included 1,750 sibships recruited into the Colon Cancer Family Registry. We also evaluated whether any associations differed by calcium supplement use, family history of CRC, or tumor characteristics. Heterogeneity by calcium and vitamin D intake was evaluated for a subset of 585 cases and 837 sibling controls who completed a detailed food frequency questionnaire. Age- and sex-adjusted associations were estimated using conditional logistic regression. Overall, we did not find evidence for an association between any single-nucleotide polymorphism (SNP) in VDR or GC and risk for CRC (range of unadjusted P values 0.01-0.98 for VDR and 0.07-0.95 for GC). None of these associations was significant after adjustment for multiple comparisons. We also found no evidence that calcium or vitamin D intake (food and supplement) from the food frequency questionnaire modified the association estimates between VDR and GC SNPs and CRC. We did observe associations between SNPs in GC and microsatellite unstable CRC, although these results should be confirmed in additional studies. Overall, our results do not provide evidence for a role of common genetic variants in VDR or GC in susceptibility to CRC.
Poynter
Jenny N
JN
Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA. poynt006@umn.edu
Jacobs
Elizabeth T
ET
Figueiredo
Jane C
JC
Lee
Won H
WH
Conti
David V
DV
Campbell
Peter T
PT
Levine
A Joan
AJ
Limburg
Paul
P
Le Marchand
Loic
L
Cotterchio
Michelle
M
Newcomb
Polly A
PA
Potter
John D
JD
Jenkins
Mark A
MA
Hopper
John L
JL
Duggan
David J
DJ
Baron
John A
JA
Haile
Robert W
RW
D002136:Calcium, Dietary; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D004032:Diet; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics*; D012042:Registries; D012307:Risk Factors; D014807:Vitamin D / Q000378:metabolism; D014809:Vitamin D-Binding Protein / Q000235:genetics*
D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D014809:Vitamin D-Binding Protein; D014807:Vitamin D