Single nucleotide polymorphisms of the EVER2 gene in squamous cell carcinomas in patients with actinic keratosis

Introduction. In recent years, two novel genes, EVER1 and EVER2, have been detected, mutations in which play a role in development of epidermodysplasia verruciformis (EV), a genodermatosis associated with squamous skin cancers (SCC). Recently it was found that polymorphism of the EVER2 gene is related to increased risk of SCC in the general population. The aim of this study was based on the hypothesis that EVER genes, mutations of which play a key role in skin cancers in EV, can also be impaired in SCC in patients with actinic keratosis (AK) in the general population.

Objective. To evaluate the association of polymorphisms rs7208422, rs35748721, rs62079073, rs112802399, rs12452890 of the EVER2 gene in SCC in patients with actinic keratosis in the general population.

Material and methods. Hundred patients with actinic keratosis were analyzed due to presence of SSC. In the study 360 persons were also included as a control group. All the participants were genotyped using real-time polymerase chain reaction (RT-PCR) with reagents from Applied Biosystems.

Results. In the group of patients with AK and coexisting SCC there was no presence of genotypes TG, TT or allele T of polymorphism rs62079073 of the EVER2 gene and the whole group had only genotype GG. Frequency of genotype GG in AK and coexisting SCC was statistically significant compared to the group of patients without coexisting SCC (100% vs. 82.9%; p = 0.01). Similarly, frequency of allele T was significantly higher in the group of patients without presence of SCC (0% vs. 10.5%; p = 0.026). Multivariate regression analysis confirmed that an independently associated factor connected with appearance of SSC in patients with actinic keratosis is genotype GG (p = 0.034).

Conclusions. Genotypes TT and TG as well as allele T of polymorphism rs62079073 of the EVER2 gene have a protective influence on the appearance of SCC in patients with AK.