Abstract
Simple SummaryUveal melanoma (UM) is the most common form of eye cancer in adults. It has a poor prognosis and limited treatment options. UM, unlike cutaneous melanoma (CM), historically lacks convincing evidence of causative ultraviolet radiation (UVR) involvement in its pathophysiology and ex vivo experimentation has suggested that UVR cannot even penetrate through the anterior ocular structures to initiate carcinogenic changes. Opposing this idea are the recent publications of UVR damage signatures in UM samples, even in those arising from the posterior uvea. This review provides an up-to-date exploration of endogenous and exogenous factors that can impact ocular susceptibility UVR, whether they form any relationship with UM risk or incidence.Uveal melanoma (UM) is currently classified by the World Health Organisation as a melanoma caused by risk factors other than cumulative solar damage. However, factors relating to ultraviolet radiation (UVR) susceptibility such as light-coloured skin and eyes, propensity to burn, and proximity to the equator, frequently correlate with higher risk of UM. These risk factors echo those of the far more common cutaneous melanoma (CM), which is widely accepted to be caused by excessive UVR exposure, suggesting a role of UVR in the development and progression of a proportion of UM. Indeed, this could mean that countries, such as Australia, with high UVR exposure and the highest incidences of CM would represent a similarly high incidence of UM if UVR exposure is truly involved. Most cases of UM lack the typical genetic mutations that are related to UVR damage, although recent evidence in a small minority of cases has shown otherwise. This review therefore reassesses statistical, environmental, anatomical, and physiological evidence for and against the role of UVR in the aetiology of UM.
Highlights
These states represent only a sub-population of the Australian continent, but the incidence of the BAP1 germline mutation is more or less comparable to results found elsewhere [8,101,114,115,116]. This suggests a common genetic susceptibility in only a small proportion of Uveal melanoma (UM) cases. This does not rule out germline genes other than BAP1 that have not yet been identified as predisposing factors, nor does it rule out the possibility that a mixture of risk factors, such as ultraviolet radiation (UVR) exposure and genetic disposition, are independently influencing the incidence of UM in a small number of cases
The Australian continent, where high UVR index and exposure already cause a higher incidence of cutaneous melanoma (CM) than much of the world, has proven to be a useful-but by no means the only-geographical area to model the possibility that UVR, focussed to a point by the optics of the eye, could impact oncogenesis
The fact remains that most UMs originate from the choroid, a posterior ocular structure, while the amount of UVR that can penetrate beyond the anterior ocular structures is essentially obsolete in adults, certainly not in children, and evidence of UVR
Summary
The quality and quantity of melanin presents as different eye colours and skin colours [4] and provide varying levels of protection from ultraviolet radiation (UVR) [5] This protection is important because UVR can cause physical or genomic damage to cells [6,7,8]. Unlike CM, UM is a rare cancer, despite being the most common primary intraocular malignant cancer in adults [13,20] It has an incidence of only 5 to 10 per million per year in Australia [21] compared to nearly 500 cases of CM per million per year [15]. RR, Risk Ratio; OR, Odds Ratio. -, No risk (RR or OR ≤ 1); +, Mild risk (RR or OR > 1 to 100 freckles. 2 ++ at 20–30◦ S but-at ≤20◦ S
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