Serum 25-Hydroxyvitamin D, Dietary Calcium Intake, and Distal Colorectal Adenoma RiskVitamin D has recently emerged as a potentially protective agent against colorectal neoplasia. We assessed the associations between dietary vitamin D, plasma 25-hydroxyvitamin D [25(OH)D], dietary calcium, and colorectal adenomas in a large screening sigmoidoscopy-based case-control study in Southern California. Because conversion of serum 25(OH)D to serum 1,25-vitamin D is highly regulated by serum calcium, we also assessed modification of the 25(OH)D-adenoma association by calcium intake. Cases were 473 subjects with a primary adenoma, and controls were 507 subjects who had no adenomas at sigmoidoscopy and no history of adenomas. Compared with those in the lowest quartile of intake, those in the highest quartile of dietary vitamin D had an adjusted odds ratio (OR) of 0.83 [95% confidence interval (CI) = 0.49-1.41] and those in the highest quartile of dietary calcium had an OR of 0.82 (95% CI = 0.49-1.25). There was a suggestion that plasma 25(OH)D may be protective in this population (OR for highest vs. lowest quartile = 0.74, 95% CI = 0.51-1.09). A significant protective effect of 25(OH)D was clearly evident only in those with calcium intakes below (OR = 0.40 for highest vs. lowest quartile, 95% CI = 0.22-0.71, p for trend = 0.005) and above (OR = 1.17, 95% CI = 0.69-1.99, p for trend = 0.94) the median calcium intake.
Genetic Variation in the Vitamin D Receptor ( <i>VDR</i> ) and the Vitamin D–Binding Protein ( <i>GC</i> ) and Risk for Colorectal Cancer: Results from the Colon Cancer Family RegistryJenny N. Poynter, Elizabeth T. Jacobs, Jane C. Figueiredo et al.|Cancer Epidemiology Biomarkers & Prevention|2010 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.
Supplementary Table 1 from Genetic Variation in the Vitamin D Receptor (<i>VDR</i>) and the Vitamin D–Binding Protein (<i>GC</i>) and Risk for Colorectal Cancer: Results from the Colon Cancer Family RegistrySupplementary Table 1 from Genetic Variation in the Vitamin D Receptor (<i>VDR</i>) and the Vitamin D–Binding Protein (<i>GC</i>) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry
Data from Genetic Variation in the Vitamin D Receptor (<i>VDR</i>) and the Vitamin D–Binding Protein (<i>GC</i>) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry<div>Abstract<p>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 (<i>VDR</i>) and the vitamin D–binding protein (<i>GC</i>; 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 <i>VDR</i> or <i>GC</i> and risk for CRC (range of unadjusted <i>P</i> values 0.01-0.98 for <i>VDR</i> and 0.07-0.95 for <i>GC</i>). 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 <i>VDR</i> and <i>GC</i> SNPs and CRC. We did observe associations between SNPs in <i>GC</i> 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 <i>VDR</i> or <i>GC</i> in susceptibility to CRC. Cancer Epidemiol Biomarkers Prev; 19(2); 525–36</p></div>
Data from Genetic Variation in the Vitamin D Receptor (<i>VDR</i>) and the Vitamin D–Binding Protein (<i>GC</i>) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry<div>Abstract<p>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 (<i>VDR</i>) and the vitamin D–binding protein (<i>GC</i>; 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 <i>VDR</i> or <i>GC</i> and risk for CRC (range of unadjusted <i>P</i> values 0.01-0.98 for <i>VDR</i> and 0.07-0.95 for <i>GC</i>). 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 <i>VDR</i> and <i>GC</i> SNPs and CRC. We did observe associations between SNPs in <i>GC</i> 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 <i>VDR</i> or <i>GC</i> in susceptibility to CRC. Cancer Epidemiol Biomarkers Prev; 19(2); 525–36</p></div>