Oküler yüzey skuamöz hücreli neoplazmlarında vitamin D reseptör polimorfizmlerinin araştırılması
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Tarih
2017
Yazarlar
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Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Oküler yüzey skuamöz hücreli neoplazmlarında (OYSHN) vitamin D reseptör (VDR) polimorfizmlerinin araştırılması, saptanan polimorfizmlerle OYSHN gelişimine yatkınlık ve klinik gidiş arasındaki ilişkinin değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: OYSHN tanısı almış 70 hasta, yaşa ve cinsiyete göre eşleştirilmiş 75 sağlıklı birey çalışmaya dahil edildi. Genetik analiz için tüm gönüllü ve hasta bireylerden 2 cc EDTA’lı kan alınarak VDR FokI ve BsmI polimorfizmleri çalışıldı. Saptanan polimorfizmlerle histopatolojik tanı, nüks oranları, tümör evresi ilişkisi araştırıldı.
Polimorfizm araştırılması yanı sıra OYSHN`li olgularda literatürde ilk olarak speküler mikroskop ile kornea endotel hücre sayımı, Scheimmpflug kamera sistemi ile kornea topografisi ve Ocular Response Analyser (ORA) cihazı ile kornea biyomekanik özellikleri değerlendirildi.
Bulgular: Histopatolojik olarak 43 olgu skuamöz hücreli karsinom (SHK), 27 olgu konjonktival intraepitelyal neoplazi (KİN) idi. VDR geni FokI polimorfizmi genotip (FF, Ff, ff) ve BsmI polimorfizmi genotip (BB, Bb, bb) sıklıkları çalışma ve kontrol grubunda benzer bulundu. FokI için polimorfizmi taşıma açısından (heterozigot (Ff) veya homozigot (ff) ) gruplar arasında fark saptanmazken, BsmI için çalışma grubunda polimorfizm sıklığı (Bb ve bb) istatistiksel olarak anlamlı derecede artmış bulundu (p=0,046). f allel sıklığı açısından gruplar arasında fark bulunmazken, b allel sıklığı çalışma grubunda fazla bulunmakla beraber istatistiksel olarak anlamlılık sınırına erişmedi (p=0,07). Tümör evresi, nüks - polimorfizm sıklığı ve hasta yaşı - polimorfizm sıklığı arasında ilişki saptanmadı.
Ayrıca çalışmamızda speküler mikroskopi ile tümörün kornea invazyonunun endotel hücre sayısını etkilediği gösterildi. Tümör eksizyonu sonrası endotel hücre sayısında ve varyasyon katsayısında anlamlı azalma bulundu. Korneal histerezis OYSHN`li gözlerde anlamlı olarak düşük saptandı, korneal rezistans faktör değeri ise bu gözlerde daha düşük izlense de istatistiksel anlamlılık sınırına erişmedi. Tümör eksizyonu öncesinde Pentacam ile değerlendirilen kornea hacmi ve santral kornea kalınlığı hasta grubunda kontrol grubuna göre anlamlı olarak daha yüksek saptandı.
Sonuç: Aktif D vitamininin VDR`ye bağlanıp hücre proliferasyonundan sorumlu genlerin regülasyonu ile kanser hücrelerinin büyümesini inhibe ettiği bilinmektedir. Bazı SHK’lerde VDR polimorfizmleri saptanmış olmakla birlikte OYSHN için bu araştırma bir ilktir. VDR genindeki BsmI polimorfizmi, özellikle bb genotipi ve b allelinin varlığı OYSHN yatkınlığı ile ilişkili gözükmektedir. VDR FokI ve BsmI gen polimorfizmlerinin OYSHN seyrinde etkili olabileceği düşünülebilir.
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.
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.
Açıklama
Anahtar Kelimeler
BsmI, Fok I, Oküler Yüzey, Polimorfizm, Skuamöz Hücreli Neoplazi, Vitamin D Reseptörü, Ocular Surface, Polymorphism, Squamous Cell Neoplasm, Vitamin D Receptor
