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]. Doseresponse 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.
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