An enhanced risk of basal cell carcinoma is associated with particular polymorphisms in the VDR and MTHFR genes.

Background: Vitamin D and folate are influenced by ultraviolet radiation (UVR), and both are implicated in skin carcinogenesis. Polymorphisms in the genes involved in the metabolism of these two compounds may alter the risk of basal cell carcinoma (BCC).

Objective: To assess the frequency of four polymorphisms in the gene encoding the vitamin D receptor (VDR) (FokI, BsmI, TaqI and ApaI) and two in the gene encoding methylenetetrahydrofolate reductase (MTHFR) (677C/T and 1286A/C) in 142 patients of Polish origin with BCC and the same number of controls. The expression of VDR and MTHFR proteins in the skin, and the vitamin D status of a subset of patients and controls were also measured.

Patients/methods: The polymorphisms were assayed by PCR-RFLP, the VDR and MTHFR proteins by immunoblotting and vitamin D status as 25-hydroxyvitamin D (25(OH)D) level in the serum by RIA.

Results: The presence of the TT genotype in the FokI VDR polymorphism resulted in a >10-fold higher risk of BCC development. The CT genotype in 677C/T MTHFR polymorphism and CC genotype in 1286A/C MTHFR polymorphism also significantly increased the risk of BCC development. The expression of the VDR and MTHFR proteins was significantly higher in BCCs of the patients than in the healthy skin of the controls. The median serum level of 25(OH)D was significantly higher in the control group compared with the patients with BCC.

Conclusions: Certain VDR and MTHFR gene polymorphisms increase the risk of BCC development in individuals of Polish origin.