Exposure to sunlight is the major source of vitamin D and the main environmental cause of non-melanocytic skin cancers. Vitamin D, partly mediated through the vitamin D receptor (VDR), has potential therapeutic applications in skin cancer. The aim of this study was to investigate the association of BsmI and ApaI VDR polymorphisms among patients with non-melanoma cancers and controls. An observational case-control study was conducted in a sample of 154 subjects. We observed no significant effects between these polymorphisms and skin cancer risk. When stratified for gender, GG and AG BsmI polymorphisms significantly increased the risk of basal cell carcinomas in males. In relation to ApaI, all three polymorphisms significantly increased the risk of basal cell carcinoma in males. When stratified for age, we found that being 70 years of age or younger was a protective factor against both skin cancers. Being a female and 70 years old or younger was a protective factor for basal cell carcinoma. A comparison of the frequencies of the VDR genotypes in patients older than 70 years vs. 70 years or younger also revealed age-dependent variations in patients with non-melanoma skin cancer. Our study suggests a role for VDR polymorphisms in non-melanoma skin cancer development.

Background Skin cancer is one of the common malignancies. There is sufficient evidence that sunlight (ultraviolet radiation) contributes to the development of skin cancer, but there is also evidence that relates adequate serum levels of vitamin D produced on the skin by the action of ultraviolet radiation with the decreased risk of various types of cancers, including skin cancer. The aim of this study was to investigate the association of vitamin D serum levels among patients with non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) and controls. Methods A prospective observational case-control study was conducted in a sample of 84 subjects in Extremadura (Spain). Forty-one patients with histologically diagnosed basal cell carcinomas and squamous cell carcinomas and 43 healthy controls were randomly chosen to assess whether vitamin D (25(OH)D3) serum level, age and sex were related to non-melanoma skin cancer and to determine the possible risk of this type of skin cancer for these variables. Results When analysing serum vitamin D levels, we ensured that all our subjects, both cases and controls, had normal or low serum vitamin D levels, even though the samples were taken during months with the highest solar irradiance in our region. It is striking in our results that there was a higher percentage of subjects with deficits of vitamin D who did not have skin cancer (66%) than patients with deficits with these types of skin cancers (34%). When adjusting the model for age and sex, vitamin D values above 18 ng/ml increased the risk of suffering from non-melanoma skin cancer by nearly 7-fold (aOR: 6.94, 95% CI [1.55–31.11], p = 0.01). Conclusions Despite the controversial data obtained in the literature, our results suggest that lower levels of vitamin D may be related to a reduced incidence of non-melanoma skin cancer.