The associations between CYP24A1 polymorphisms and cancer susceptibility: A meta-analysis and trial sequential analysis.

Purpose: Published data have shown that vitamin D may have a protective effect on cancer development. CYP24A1, the main enzyme responsible for the degradation of active vitamin D, plays an important role in many cancer related cellular processes. Up to now, relationships between CYP24A1 polymorphisms and cancer susceptibility have been widely investigated, whereas the results are inconsistent. The aim of present meta-analysis was to explore the associations between CYP24A1 polymorphisms and cancer susceptibility.

Methods: We searched on EMBASE, Web of Science, PubMed and China National Knowledge Infrastructure (CNKI) electronic databases (up to July 1, 2017) for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to make the evaluation clear.

Results: Twenty-nine studies published in eight publications involving 20,593 cases and 25,458 controls were included. Five CYP24A1 gene polymorphisms were evaluated: rs2181874, rs2585428, rs4809960, rs6022999, and rs6068816. Our analyses suggested that rs2585428 and rs4809960 polymorphisms were significantly associated with overall cancer risk. Stratification analyses of ethnicity indicated that rs2585428 and rs4809960 polymorphisms decreased the risk of cancer among Caucasians. When studies were stratified by cancer type, our results indicated that rs2585428 significantly decreased the risk of pancreas cancer, while rs4809960 significantly decreased the risk of breast cancer. There were no associations of rs2181874, rs6022999, or rs6068816 with overall cancer risks.

Conclusion: Associations between CYP24A1 polymorphisms and cancer risks were examined, and additional multi-center studies with large samples are necessary to validate our results.