Meta-analysis of vitamin D-binding protein and cancer risk

Cancer Epidemiol Biomarkers Prev. 2015 Nov;24(11):1758-65. doi: 10.1158/1055-9965.EPI-15-0262. Epub 2015 Sep 12.


Background: Epidemiologic evidence supported a role for vitamin D and vitamin D receptor (VDR) polymorphisms in cancer risk. Beyond VDR, the biologic effects of vitamin D are mediated by the vitamin D-binding protein (DBP), a key protein in vitamin D metabolism. Furthermore, the gene encoding the DBP (GC, group-specific component) has an important role in the vitamin D pathway. Several studies investigated DBP serologic levels and GC polymorphisms in association with cancer risk with controversial results. Thus, we carried out a meta-analysis to investigate these associations.

Methods: We included 28 independent studies concerning the following tumors: basal cell carcinoma, bladder, breast, colon-rectum, endometrium, liver, esophagus, stomach, melanoma, pancreas, prostate, and kidney. Through random-effect models, we calculated the summary odds ratios (SOR) for serum DBP and the GC polymorphisms rs2282679, rs12512631, rs7041, rs4588, rs17467825, rs1155563, and rs1352844.

Results: We found a borderline decrease in cancer risk for subjects with high compared with low levels of DBP [SOR, 0.75; 95% confidence interval (CI), 0.56-1.00]. Dose-response meta-analysis indicates a nonsignificant decrease risk for an increase of 1,000 nmol/L of DBP (SOR, 0.96; 95% CI, 0.91-1.01). We found no significant alterations in cancer risk for subjects carrying any of the studied GC polymorphisms compared with wild-type subjects both in the main analysis and in analyses stratified by cancer type and ethnicity.

Conclusions: We found trends toward significance, suggesting a role of DBP in cancer etiology, which should be confirmed in further studies.

Impact: To our knowledge, this is the first study to investigate GC polymorphisms and DBP serologic levels in association with any type of cancer.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Neoplasms / blood
  • Neoplasms / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Vitamin D-Binding Protein / blood
  • Vitamin D-Binding Protein / genetics*


  • Vitamin D-Binding Protein