Oncologic Implications of Genetic and Epigenetic Basis of Pterygium

Pterygium is a fast-growing hyperplastic growth from the conjunctiva over the limbus towards the central cornea. Although the exact pathological mechanism remains to be elucidated, it is strongly associated with the exposure to ultraviolet light. On the contrary, the contribution of cigarette smoking to the incidence of primary pterygium is inconsistent. Despite the fast-growing nature of pterygium, high expression of p53 has been consistently reported by multiple investigations. Recently, we reported the contribution of p53-binding protein MDM2 to the suppression of the p53-mediated apoptosis in human pterygium. Disruption of the MDM2-p53 interaction by Nutlin treatment showed specific killing of pterygium cells with low toxicity to conjunctiva cells. We also identified the involvement of the growth hormone-releasing hormone signaling pathway in the pathogenesis of pterygium. In addition, our recent meta-analysis identified a negative correlation of cigarette smoking with the occurrence of pterygium in current smokers. Major components of the cigarette smoke, including nicotine and cotinine, suppressed primary pterygium cell proliferation and migration, possibly through extracellular matrix remodeling and epithelial-to-mesenchymal transition. Our results underline the genetic and epigenetic basis of pterygium, which broadens the understanding of the oncologic-like properties of pterygium.