Investigation of vitamin D receptor polymorphisms in ocular surface squamous cell neoplasms

Objective: The purpose of this study is to investigate vitamine D receptor (VDR) polymorphisms in ocular surface squamous cell neoplasms (OSSN), and to evaluate the relationship between the identified polymorphisms and susceptibility to OSSN and clinical course. Materials and Methods: Seventy patients with OSSN and 75 healthy age and gender matched individuals were included in the study. For genetic analysis, 2 cc blood containing EDTA was drawn from all volunteers and patient subjects and VDR FokI and BsmI polymorphisms were examined. The relationships between histopathological diagnosis, recurrence rates, tumor stage, and identified polymorphisms were investigated. In addition to polymorphisms, corneal endothelial cell count with specular microscope, corneal topography with Scheimmpflug camera system and corneal biomechanical properties with ORA (Ocular response analyzer) device were assessed in OSSN cases for the first time in the literature. Findings: Histopathologically, 43 of the cases were squamous cell carcinoma (SCC) and 27 of the cases were conjunctival intraepithelial neoplasia (CIN). The frequency of FokI (FF, Ff, ff) and BsmI (BB, Bb, bb) polymorphism genotype of VDR gene were similar in the study and control groups. The frequency of polymorphism (Bs and bb) for BsmI increased significantly (p = 0.046) in the study group, while no difference was found between the groups in terms of polymorphic carriers (heterozygous or homozygous) for FokI. While there was no difference between the groups in terms of frequency of f allele, the frequency of b allele was higher in the study group, however it did not reach the statistical significance limit (p = 0.07). There was no correlation between tumor stage, recurrence-polymorphism frequency and patient age-polymorphism frequency. In addition, the present study showed that corneal invasion of OSSN affected the number of endothelial cells as measured with specular microscopy and coefficient of variation was significantly higher in the patient group compared to the control group. There was a significant decrease in endothelial cell count and coefficient of variation after the excision of tumor. Corneal hysteresis was significantly lower in eyes with OSSN and corneal resistance factor value was lower and not statistically significant in these eyes. Corneal volume and central corneal thickness assessed by Pentacam before tumor excision were significantly higher in the patient group compared to the control group. Conclusion: It is known that active vitamin D inhibits the growth of cancer cells by binding to VDR with regulation of genes responsible for cell proliferation. Even though VDR polymorphisms were identified in some SCCs this study is the first for OSSN. The presence of BsmI polymorphism in VDR, in particular bb genotype and b allele, appears to be associated with the susceptibility of OSSN. FokI and BsmI gene polymorphisms of VDR have been shown to be effective in the course of OSSN.