Association between vitamin D receptor polymorphism and breast cancer in women: An umbrella review of meta-analyses of observational investigations

This study aimed to conduct an umbrella review of meta-analyses to synthesize the existing evidence regarding the relationship between vitamin D receptor (VDR) polymorphism and breast cancer (BC) risk. A comprehensive search was performed across multiple databases, including Embase, PubMed, Scopus, the Cochrane Database of Systematic Reviews, and the Web of Science. The investigation included 17 meta-analyses for the BsmI polymorphism, 6 for the Cdx2 polymorphism, and 6 for the Poly (A) polymorphism. Among the 119 datasets analyzed, only 6 (5 %) reported statistically significant outcomes (p < 0.05), comprising 2 comparisons for VDR BsmI polymorphism (3 %), 1 for VDR Cdx-2 polymorphism (4 %), and 3 for VDR Poly (A) polymorphism (14 %), across various genetic models. Notably, significant heterogeneity was observed in 82 comparisons, and publication bias was detected in 16 comparisons. Furthermore, a substantial proportion (86 %) of the included studies exhibited critically low methodological quality. In conclusion, our findings suggest that VDR polymorphism (BsmI, Cdx-2, and Poly (A)) is not strongly associated with BC risk in the general population.