Associations between serum vitamin D biomarkers and tumor expression of Ki67, p53, and COX-2 in colorectal cancer cases from the Southern Community Cohort Study

J Steroid Biochem Mol Biol. 2023 Jan:225:106201. doi: 10.1016/j.jsbmb.2022.106201. Epub 2022 Oct 6.

Abstract

Higher 25-hydroxyvitamin D is associated with lower colorectal cancer (CRC) risk, with limited data from African Americans (AAs), who have greater risk for CRC and 25-hydroxyvitamin D deficiency. In a predominantly AA sample of CRC cases from the Southern Community Cohort Study (SCCS), we report associations between vitamin D biomarkers and tumor expression of proteins implicated in vitamin D's anti-tumorigenic pathways (e.g. proliferation and inflammation) and CRC prognosis. SCCS participants with incident CRC were identified via state cancer registries. Serum 25-hydroxyvitamin D and vitamin D binding protein (VDBP) were measured at enrollment. 'Free' 25-hydroxyvitamin D was calculated via standard equation. Cellular Ki67, p53, and COX-2 were measured from tumor samples and categorized using literature-defined cut-points related to survival. Generalized linear models were used to measure associations between vitamin D exposures, tumor biomarkers, and stage. In total, 104 cases (40-79 years) were analyzed. 25-hydroxyvitamin D was not associated with high Ki67 (odds ratio (OR) per 1-standard deviation (SD) increase [95% confidence interval] 1.35[0.86-2.11]), p53 (0.75[0.47-1.20]), or COX-2 expression (1.25[0.78-2.01]), or metastatic disease (1.04[0.59-1.81]). Mean biomarker expression was unrelated to 25-hydroxyvitamin D (p-trend ≥.09). Null associations were observed for VDBP and free 25-hydroxyvitamin D. In AAs (n = 70), higher VDBP was associated with lower odds of high Ki67 expression (0.53[0.28-0.98], p-trend =.04). In conclusion, we observed no associations between 25-hydroxyvitamin D and prognostic marker expression in CRC. An inverse association between VDBP and tumor Ki67 in AAs is consistent with reports showing relationships with reduced CRC mortality.

Keywords: African Americans; Colon cancer; Rectal cancer; Vitamin D; Vitamin D binding protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biomarkers
  • Calcifediol
  • Cohort Studies
  • Colorectal Neoplasms*
  • Cyclooxygenase 2 / genetics
  • Humans
  • Ki-67 Antigen / genetics
  • Tumor Suppressor Protein p53*
  • Vitamin D-Binding Protein
  • Vitamins

Substances

  • Cyclooxygenase 2
  • Tumor Suppressor Protein p53
  • Ki-67 Antigen
  • Vitamin D-Binding Protein
  • Calcifediol
  • Vitamins
  • Biomarkers