The Role of UVA in Skin Cancer
While it was once thought that UVB was the prime culprit of skin cancers, a new study undertaken by Professor Gary Halliday's research team at the Sydney Cancer Centre at Royal Prince Alfred Hospital and the University of Sydney suggests that the role of UVA in causing skin damage leading to skin cancer has been severely underestimated.
Speaking at The Royal College of Pathologists of Australasia's (RCPA) 11th annual Pathology Update conference at the Sydney Convention Centre in Darling Harbour, Prof Halliday says his research team has proven that UVA is not just a contributing factor, but is in fact, the dominant mutagen in the basal layer of the epidermis, which contains the dividing cells that cause skin cancer.
Ultraviolet (UV) radiation within sunlight is the prime cause of skin cancer in humans. Both mutagenic and immunosuppressive, they also cause severe disruption to cell cycles, causing widespread genetic damage.
However, of the major kinds of UV radiation, UVA and UVB are the only ones able to penetrate the atmosphere, causing conditions such as premature aging, skin cancers and eye damage.
While UVB is directly absorbed by DNA causing photolesions such as pyrimydine dimers (CPD), UVA is absorbed by unknown chromophores, causes reactive oxygen species and inflicts oxidative damage to DNA, proteins and lipids.
"The reason why UVA is so effective in causing cancer appears to be due to lower levels of DNA repair in these basal keratinocytes and deeper penetrance of UVA than UVB to these cells.
According to Prof Halliday, the basal layer of the human skin is especially susceptible to UVA-induced genetic damage as it has low expressions of hOGG1, a major enzyme which repairs oxidised guanine (8-oxoG), the main photodamage caused by UVA.
The average penetration of UVA into the skin is also much deeper than that of UVB at 320-400mm and 290-320nm respectively.
'We have recently discovered a novel hotspot mutation in the chromatin remodelling gene, the exon-4 of BRM in human skin tumours, which is consistent with that being caused by UVA," says Prof Halliday.
"Our recent action spectrum shows two immunosuppressive peaks, one in the UVB range at 300 nm and a second in the high wavelength UVA at 370 nm with wavelengths between these peaks being less effective. This adds to the accumulating evidence that the role of UVA in causing skin cancer in humans has been underestimated."
In high erythemal doses of sunlight, for example during recreational activities, it is UVB that suppresses immunity, not UVA. However in low dose sunlight, for example during normal day activities, it is quite evident that UVA is causing the most damage to the skin's immune system.
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Professor Gary Halliday is Professor of Dermatology at the University of Sydney. He obtained his PhD from Monash University in 1981 and his Doctor of Science from the University of Sydney in 2001. His research is directed towards understanding the role of sunlight in skin carcinogenesis; particularly ultraviolet radiation suppression of immunity, induction of gene mutations, skin cancer cell biology and development of effective prevention.
His research group is part of the Sydney Cancer Centre, the Bosch Institute, the department of Dermatology of Royal Prince Alfred Hospital, and the Central Clinical School of the University of Sydney. He has 191 publications, has supervised 66 research students who have been awarded degrees and has been invited as a guest speaker to 79 conferences.