A study looking at UV exposure and genetic risks in relation to melanoma

Melanomas are common cancers among people of European ancestry, accounting for 1·6% of all new cancer cases and 0·6% of all cancer deaths worldwide in 2018. The only environmental factor consistently implicated as a cause of melanoma is ultraviolet (UV) radiation, but the relationship is complex, and little is known about how genetic factors influence the association between UV and melanoma. The effects of UV exposure are affected by ‘host factors’ (meaning factors that are specific to the individual, such as their genes), and by ‘host behaviours’ (such as their patterns of sun exposure and history of sunburns). The aim of this study was to examine whether melanoma risk varies according to reported levels of sun exposure, even within populations exposed to year‐round high levels of sunlight (i.e. Queensland, Australia). More particularly, the authors sought to determine whether the associations with sunlight differ according to a person's inherent genetic risk. In a large Australian study, country of birth, age at migration and sunburns during all periods of life were all strongly associated with melanoma risk. People who had a past history of other types of skin cancer (specifically, BCC or SCC) and of other skin lesions caused by sun exposure had a higher risk of developing melanoma than people without sun‐related skin lesions. The authors found evidence for gene‐environment interactions that are consistent with the ‘divergent pathway’ hypothesis for melanoma development, which almost 20 years ago proposed that people with a high genetic susceptibility (i.e. at higher risk of melanoma, genetically) may only need modest levels of sun exposure to trigger melanoma development, whereas those with low genetic susceptibility require continued high levels of sun exposure to trigger melanoma development. In line with this hypothesis, the authors found that people who were at low genetic risk for melanoma, but who did eventually develop melanoma, were more likely to have been treated for sun‐related skin lesions than people at high genetic risk. In other words, the people at low genetic risk who developed melanoma appeared to need a much larger dose of sun exposure than those at high genetic risk. In contrast, among people at high genetic risk, markers of high‐level early life ambient exposure were relatively more important. These findings may help to identify and inform people at high risk of melanoma who stand to benefit most from adopting sun protective behaviours. Linked Article:   Olsen et al. Br J Dermatol 2020; 183 :303–310.