Role of VDR gene polymorphisms and environmental factors in the development of skin cancers: evidence by updated meta-analysis.

The vitamin D and its receptor the VDR have pleiotropic effects on different biological mechanisms, including skin cancers. The sun UV radiation has confirmed effects on both skin cancers and on VD/VDR pathways. We aim to investigate the role of the VDR and its interaction with specific environmental factors to develop skin cancers. We conducted meta-analyses of published association studies on the VDR gene polymorphisms FokI, BsmI, TaqI and AapI and skin cancers. Subgroup analyses were performed to investigate the impact of environmental factors on skin cancers. Meta-analysis showed that the VDR Fok I polymorphism was associated with melanoma risk (CT vs. CC + TT, P = 0.020), with CT genotype as a significant risk factor. We found also significant association for the VDR BsmI polymorphism (AG vs. GG model, P = 0.020), as AG genotype having a protective effect against melanoma. However the VDR TaqI and ApaI polymorphisms were not associated with melanoma in the overall analysis. Met-analysis of studies on non-melanoma cancers (NMSC) showed significant effects of FokI (TT vs. CT + TT, P = 0.002, CC vs. CT, P = 0.017 and CC vs. TT, P = 0.001), with TT genotype as a risk factor, whereas the CC genotype was protective against NMSC. The TaqI showed also significant association with NMSK (T vs. C contrast allele: P = 0.006 and TT vs. CT + CC, P = 0.011), with T allele and TT genotype as having protective roles. Stratification according to geographic localisation showed that the FokI CC genotype had protective effect in both North America (CC vs. CT + TT, P = 0.003) and North Europe (CC vs. CT + TT, P = 0.010). Stratification according to the study period revealed that the FokI CT genotype had a highly significant risk (CT vs. TT, P < 0.001) in the last decade 2011-2020. VDR FokI and BsmI polymorphisms showed significant associations with melanoma, whereas FokI and TaqI were significantly associated with NMSC. Subgroup analysis revealed that factors such as the geographic localisation and study period influenced the association between the VDR gene and the risk of skin cancers.