The Impact of Ultraviolet Radiation on the Aetiology and Development of Uveal Melanoma

Abstract

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.

Differences in Uveal Melanoma Age-Standardized Incidence Rates in Two Eastern States of Australia Are Driven by Differences in Rurality and Ultraviolet Radiation

“…Firstly, south-to-north latitude trends, higher rural ASR, and the substantially greater ASR of anterior UM in QLD than in VIC may all suggest a relationship between UM ASR and UVR in a proportion of cases. This agrees with anatomical, molecular, and epidemiological evidence that at least a small portion of UM cases are UVR-related [ 34 ].…”

“…The higher ASR of UM in QLD and rural communities is therefore consistent with a hypothesis of UVR-induced UM. This is strengthened by the fact that the differences in ASRs are greater for anterior UMs: The anterior uveal structures (ciliary body and iris) do not have the protection of the UVR-absorbing lens like the posterior (choroidal) uvea, thus may be more likely to be susceptible to UVR carcinogenic changes [ 33 , 34 ].…”

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

“…Over the past years, numerous risk factors have been described as being associated with the development of UM ( Figure 1 ), of which the most established are an age between 50 and 70 years, a fair skin colour, light-coloured eyes (blue or grey), multiple skin naevi, sensitivity to sunburn, northern European ancestry, congenital ocular melanocytosis, ocular melanocytoma, family history of cutaneous melanoma or UM, BAP1 (BRCA1-associated protein 1)-tumour predisposition syndrome and also germline mutations in MBD4 (methyl-CpG-binding domain protein 4), MLH1 (mutL homolog 1) and PALB2 (partner and localizer of BRCA2) [ 1 , 9 , 25 , 26 , 27 ]. Interestingly, in UM there is no evidence of gene signatures indicative of tumours induced by ultraviolet (UV) irradiation, with the only exception being iris melanoma and some residual cases of posterior melanomas [ 28 , 29 , 30 ].…”

Histopathologic and MR Imaging Appearance of Spontaneous and Radiation-Induced Necrosis in Uveal Melanomas: Initial Results

“…Uveal tract melanoma is considered a rare neoplasm, although it represents the most prevalent type of ocular melanoma and the most widespread primary intraocular malignancy among the adult population [ 1 , 2 , 3 , 4 ]. A variety of risk factors related to the onset of uveal melanoma have been identified: fair skin phototype, light iris, ultraviolet-B radiation exposure, melanocytic lesions both ocular or cutaneous, occupational cooking, welding [ 5 , 6 , 7 ].…”