BsmI polymorphism of vitamin D receptor gene and cancer risk: a comprehensive meta-analysis

The VDR gene is an important regulator of the vitamin D pathway, and the role of some of its polymorphisms on cancer risk was previously investigated. A trend of cancer risk reduction with the VDR BsmI B allele was observed for many cancer sites. We performed a comprehensive meta-analysis to investigate the role of VDR BsmI polymorphism on cancer risk, even according to different ethnicities. Summary odds ratios (SORs) were calculated with random-effects models and maximum likelihood estimation. We categorized studies into three groups ("moderate", "high" and "very high confidence") according to departure from Hardy-Weinberg equilibrium in controls, reported minor allele frequency and genotyping quality controls. The meta-analysis included 73 studies with 45,218 cases and 52,057 controls. We found a significant 6-7% reduction of cancer risk at any site respectively for carriers of Bb genotype (SOR; 95%CI: 0.94; 0.90-0.99) and for carriers of BsmI BB genotype (SOR; 95%CI: 0.93; 0.89-0.98) compared to bb carriers, and they remain statistically significant when we restricted the analysis to at least "high confidence" studies. For skin cancer, a significant risk reduction was observed for Bb carriers (SOR; 95%CI: 0.86; 0.76-0.98). We also found a significant reduction of colorectal cancer risk for BB and Bb+BB genotypes carriers, but these SORs were no more significant when we restricted the analysis to studies with "high confidence". When the analysis was stratified by ethnicity, we still observed a significant decreased risk for both Bb and BB compared to bb genotype among Caucasians: SORs (95%CI) for any cancer site were 0.97 (0.93-1.00) and 0.95 (0.91-0.99), respectively. Among other ethnic groups the inverse association was still present, but did not reach statistical significance. In conclusion, we suggest a weak effect of BsmI B allele in reducing cancer risk at any site, especially of the skin.