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Vitamin D and Actinic Keratoses

Individual susceptibility to development of actinic keratoses is influenced, in part, by polymorphisms in the gene that encodes for the vitamin D receptor.

The active form of vitamin D — 1,25-dihydroxyvitamin D — inhibits the growth of many kinds of tumors by binding to the vitamin D receptor and influencing gene transcription. The gene for the vitamin D receptor, VDR, has polymorphisms that can encourage or discourage transcriptional activity when the receptor is occupied, thereby augmenting or decreasing vitamin D’s inhibitory effects on tumor growth. Because actinic keratoses (AKs) are tumors, and because vitamin D plays a role in prevention of skin cancer, polymorphisms of VDR may influence individual susceptibility to developing AKs.

In an Australian skin cancer study, researchers genotyped the VDR polymorphisms ApaI, TaqI, and FokI in 380 people, 190 of whom had one or more AKs at the time of examination. Subjects with and without AKs were matched for age, sex, and ethnicity. The researchers found a significant difference in AK prevalence in individuals with the TaqI polymorphism (P=0.008). In both the ApaI and TaqI polymorphisms, genotypic differences were significantly associated with the prevalence of AKs and the propensity to sunburn. Specifically, heterozygous genotypes, in conjunction with skin color and ability to tan, appeared to confer protection from AKs.

Comment: Ultraviolet radiation causes skin cancer, but it also causes production of vitamin D, which inhibits tumor development. Now, we find that the situation is additionally complicated by polymorphisms of the vitamin D receptor gene. The authors of a recent meta-analysis of six studies concluded that various polymorphisms of VDR were associated with increased risk for melanoma.

— Mark V. Dahl, MD

Published in Journal Watch Dermatology October 24, 2008

Citation(s):

Carless MA et al. Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin. Br J Dermatol 2008 Sep; 159:804.

• Medline abstract (Free)

Mocellin S and Nitti D. Vitamin D receptor polymorphisms and the risk of cutaneous melanoma: A systematic review and meta-analysis. Cancer 2008 Nov; 113:2398.

• Medline abstract (Free)