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

• Published in: American journal of epidemiology Vol. 187; no. 9; pp. 1923 - 1930
• Main Authors: Gibbs, David C, Fedirko, Veronika, Um, Caroline, Gross, Myron D, Thyagarajan, Bharat, Bostick, Roberd M
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.09.2018; Oxford Publishing Limited (England)
• Subjects: 25-Hydroxyvitamin D; Adenoma; Adenoma - blood; Adenoma - genetics; Adult; Aged; Calcifediol - blood; Calciferol; Case-Control Studies; Colon; Colorectal cancer; Colorectal Neoplasms - blood; Colorectal Neoplasms - genetics; Confidence intervals; Female; Humans; Isoforms; Male; Middle Aged; Original Contributions; Protein Isoforms; Proteins; Risk; Statistical analysis; Tumors; Vitamin D; Vitamin D-binding protein; Vitamin D-Binding Protein - genetics; colorectal neoplasms; vitamin D; vitamin D–binding protein; gene-environment interaction; case-control studies
• ISSN: 0002-9262; 1476-6256; 1476-6256
• DOI: 10.1093/aje/kwy102

Abstract Concentration of 25-hydroxyvitamin D3 (25(OH)D3), the main circulating form of vitamin D, is inversely associated with incident, sporadic colorectal adenoma risk. We investigated whether this association differs by 2 functional variants in the vitamin D–binding protein (DBP) gene, group-specific component (GC), that encode for common protein isoforms Gc1s, Gc1f, and Gc2 linked to differences in vitamin D metabolism. We pooled data (418 patients with adenoma and 524 polyp-free control subjects) from 3 colonoscopy-based case-control studies (Minnesota, 1991–1994; North Carolina, 1994–1997; South Carolina, 2002). We estimated 25(OH)D3–adenoma associations, stratified by DBP isoforms, using multivariable logistic regression. Higher 25(OH)D3 concentrations were inversely associated with colorectal adenoma risk 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 for interaction = 0.03). Thus, the vitamin D–incident, sporadic colorectal adenoma association may differ by common DBP isoforms, and patients with the Gc2 isoform may particularly benefit from maintaining higher circulating 25(OH)D3 concentrations for adenoma prevention.