Variations of individual susceptibility to UV: Insights from population-based studies

Background: from a public health standpoint, the motivation for measuring phenotypic differences in risk of melanoma arises firstly because of the need to target individuals at highest risk, and secondly because it is possible that risk varies by skin type. Commonly used indicators of phenotype include those which may have been used as proxies of density or type of melanin (eye colour, hair colour and skin colour), those which are also outcomes of exposure to ultraviolet radiation (freckling and the presence of naevi), those based on answers to questions about whether individuals tan or burn when exposed to the sun (skin type), and recently-discovered genetic markers. Methods: we examine the data from published studies on factors that may determine differences in risk of melanoma from UVR exposure in Caucasian populations, present new data on the associations of melanin density in skin biopsy samples from 41 adults with commonly-used indicators of phenotype, and compute the sensitivity and specificity of these indicators as tests for high naevi densities in 14-15 year olds. Results: pooled ratios of odds of melanoma for common phenotype indicators were lowest for eye colour and hair colour, intermediate for skin type and skin colour, and highest for freckling and naevi. Skin melanin was weakly associated with eye and hair colour, freckling and naevi. The correlations of skin colour and skin type with melanin density were much higher, but even these measures had low sensitivity in testing for high naevi densities in teenagers. A combination of measures did not substantially improve sensitivity. Conclusion: commonly used phenotype indicators have limited clinical value in screening for individual risk. Future developments in measuring melanin density non-invasively or in characterising the type of melanin may produce improved discrimination. Advances in the identification of genetic markers may provide a similar opportunity.