Meta-analysis on vitamin D receptor and cancer risk: focus on the role of TaqI, ApaI, and Cdx2 polymorphisms

Vitamin D plays a significant role in our health, including cancer incidence and mortality. Vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) may affect its activity, influencing the risk of cancer. Several studies have investigated VDR SNPs, but the association with the risk of cancer is controversial. Here, we present a meta-analysis to assess the association of TaqI, ApaI, and Cdx2 SNPs with the risk of cancer. A systematic literature search was performed following a predefined protocol and using validated search strategies. This meta-analysis shows the summary odd ratio (SOR) overall, by cancer sites and by ethnicity. Up to January 2014, we identified 73 independent studies with 35525 cases and 38675 controls. The meta-analysis of Cdx2 gg versus GG showed a significant 12% increased risk for all cancers [SOR=1.12; 95% confidence interval (CI): 1.00-1.25]. The other SNPs analyzed did not show an overall significant association with the risk of cancer: SOR=0.98 (95% CI: 0.90-1.07) and 1.06 (95% CI: 0.95-1.19) for TaqI tt versus TT and ApaI aa versus AA, respectively. TaqI shows a significant 43% increased risk for colorectal cancer (SOR=1.43; 95% CI: 1.30-1.58 for tt vs. TT). Strong frequency variations are present among different ethnic groups. This meta-analysis showed an overall increased risk of cancer associated with Cdx2 SNP and a specific higher risk of colorectal cancer associated with the TaqI polymorphism. The VDR genotype might become more relevant when clustered in a specific haplotype, associated with other SNPs of genes involved in vitamin D metabolism, or for specific tumors and/or patient characteristics.