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

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.