Vitamin D Pathway Gene Polymorphisms and Keratinocyte Cancers: A Nested Case-Control Study and Meta-Analysis.

BACKGROUND: The vitamin D endocrine system is implicated in skin carcinogenesis and polymorphisms in genes associated with the vitamin D receptor (VDR) gene may alter the risk of keratinocyte cancers (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)). MATERIALS AND METHODS: In a nested case-control study of 1,124 adults, we investigated associations between polymorphisms in VDR-related pathways and incident keratinocyte cancers during 11 years of follow-up using adjusted multivariate regression analysis. We also performed a meta-analysis of rs2228570, rs7975232, rs1544410 and rs739837 polymorphisms. RESULTS: A total of 286 BCCs and 161 SCCs were newly-diagnosed during follow-up. Participants with rs2228570 and rs927650 recessive genotypes had a decreased risk of SCC (odds ratio (OR)=0.34, 95% confidence interval (CI)=0.17-0.68; OR=0.48, CI=0.27-0.84, respectively). Meta-analysis showed a lower SCC risk in rs1544410 recessive genotypes (summary OR (SOR)=0.74, CI=0.53-0.94), while rs7975232 and rs739837 recessive genotypes were associated with a decreased BCC risk (SOR=0.74, CI=0.56-0.98; SOR=0.65, CI=0.43-0.88). CONCLUSION: Our meta-analysis indicated that vitamin D receptor polymorphisms may be associated with the risk of keratinocyte cancers.