Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin.

BACKGROUND Vitamin D has a range of biological effects including antiproliferative functions that are mediated through its receptors, encoded by the VDR gene. OBJECTIVES We investigated polymorphisms within the VDR gene for association with solar keratosis (SK), a biomarker for skin cancer, and examined interactions with skin phenotype. METHODS Among participants of the community-based Nambour Skin Cancer Study, we genotyped 190 people with SKs and 190 without for ApaI, TaqI and FokI polymorphisms. RESULTS We found a significant difference in genotype frequencies of the TaqI polymorphism between affected and unaffected populations (P = 0.008). The TT/tt genotype group was associated with a twofold increase in odds of being affected by one or more SK. Individuals with fair skin and the TT/tt genotype had about a sevenfold increase, whereas fair-skinned people with the Tt genotype had a fourfold increase in odds of being affected by SK. Individuals with the TT/tt genotype who were prone to burn and not tan on acute sun exposure had about a sixfold increase in odds of SK. Fair-skinned people with VDR-Apa AA/aa genotypes had about an eightfold increase in odds of being affected by SK compared with a fivefold increase in individuals with the Aa genotype and fair skin. CONCLUSIONS The trend for homozygote genotypes to increase the odds of SK suggests that intermediate VDR activity is important in protection or that the heterodimer formed by a heterozygous genotype may have an altered binding potential. Overall, these analyses indicate that VDR may be important in SK development.