Associations of Circulating 25-Hydroxyvitamin D3 Concentrations With Incident, Sporadic Colorectal Adenoma Risk According to Common Vitamin D Binding Protein Isoforms

Abstract

25-hydroxyvitamin D₃ (25[OH]D₃), the main circulating form of vitamin D, is inversely associated with incident, sporadic colorectal adenoma. We investigated whether this association differs by two functional variants in the vitamin D binding protein gene (group-specific component, GC) that encode for common protein isoforms (Gc1s, Gc1f, Gc2) linked to differences in vitamin D metabolism. We pooled data (418 adenoma cases, 524 polyp-free controls) from three colonoscopy-based case-control studies (Minnesota, 1991–1994; North Carolina, 1994–1997; South Carolina, 2002). We estimated 25(OH)D₃-adenoma associations, stratified by vitamin D binding protein isoforms, using multivariable logistic regression. Higher 25(OH)D₃ concentrations were inversely associated with colorectal adenoma among those with the Gc2 isoform (per 10 ng/mL increase in 25(OH)D₃ odds ratio = 0.71; 95% confidence interval: 0.56, 0.90), but not among those with only Gc1 isoforms (odds ratio = 1.07; 95% confidence interval: 0.87, 1.32) (P_interaction = 0.03). These novel findings suggest that the vitamin D-incident, sporadic colorectal adenoma association may differ by common vitamin D binding protein isoforms, and that those with the Gc2 isoform may particularly benefit from maintaining higher circulating 25(OH)D₃ concentrations for adenoma prevention.