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

Jenny N. Poynter, Elizabeth T Jacobs, Jane C. Figueiredo, Won H. Lee, David V. Conti, Peter T. Campbell, A. Joan Levine, Paul Limburg, Loic Le Marchand, Michelle Cotterchio, Polly A. Newcomb, John D. Potter, Mark A. Jenkins, John L. Hopper, David J. Duggan, John A. Baron, Robert W. Haile

Research output: Contribution to journalArticle

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Abstract

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 singlenucleotide 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.

Original languageEnglish (US)
Pages (from-to)525-536
Number of pages12
JournalCancer Epidemiology Biomarkers and Prevention
Volume19
Issue number2
DOIs
StatePublished - Feb 2010

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Vitamin D-Binding Protein
Calcitriol Receptors
Colonic Neoplasms
Registries
Colorectal Neoplasms
Vitamin D
Calcium
Single Nucleotide Polymorphism
Gene Components
Food
Dietary Supplements
Microsatellite Repeats
Logistic Models

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

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. / Poynter, Jenny N.; Jacobs, Elizabeth T; Figueiredo, Jane C.; Lee, Won H.; Conti, David V.; Campbell, Peter T.; Levine, A. Joan; Limburg, Paul; Le Marchand, Loic; Cotterchio, Michelle; Newcomb, Polly A.; Potter, John D.; Jenkins, Mark A.; Hopper, John L.; Duggan, David J.; Baron, John A.; Haile, Robert W.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 19, No. 2, 02.2010, p. 525-536.

Research output: Contribution to journalArticle

Poynter, JN, Jacobs, ET, Figueiredo, JC, Lee, WH, Conti, DV, Campbell, PT, Levine, AJ, Limburg, P, Le Marchand, L, Cotterchio, M, Newcomb, PA, Potter, JD, Jenkins, MA, Hopper, JL, Duggan, DJ, Baron, JA & Haile, RW 2010, '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', Cancer Epidemiology Biomarkers and Prevention, vol. 19, no. 2, pp. 525-536. https://doi.org/10.1158/1055-9965.EPI-09-0662
Poynter, Jenny N. ; Jacobs, Elizabeth T ; Figueiredo, Jane C. ; Lee, Won H. ; Conti, David V. ; Campbell, Peter T. ; Levine, A. Joan ; Limburg, Paul ; Le Marchand, Loic ; Cotterchio, Michelle ; Newcomb, Polly A. ; Potter, John D. ; Jenkins, Mark A. ; Hopper, John L. ; Duggan, David J. ; Baron, John A. ; Haile, Robert W. / 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. In: Cancer Epidemiology Biomarkers and Prevention. 2010 ; Vol. 19, No. 2. pp. 525-536.
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abstract = "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 singlenucleotide 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.",
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