Defining critical aspects of environmental ultraviolet exposure in melanogenesis

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DESCRIPTION (provided by applicant): Sun exposure has been consistently implicated in the development of non-melanoma skin cancers, but its role in melanoma etiology remains controversial, and is complicated by poorly understood genetic and behavioral factors. Melanoma incidence continues to increase (it is now the 4th most common cancer among males in California). Efforts to reduce melanoma incidence through sun exposure avoidance have had limited success, underscoring our lack of understanding of the true mechanisms of melanogenesis. Melanoma epidemiology is based on retrospective studies: recall bias probably explains associations between sunburn (almost always self-reported) and melanoma. Moreover, sun burn represents only excessive exposure to solar radiation, while sun-induced DNA damage potentially occurs across all levels of intensity: there is no accepted method for directly measuring sun exposure in epidemiological studies. In order to better understand the etiology of melanoma (particularly the role of sun exposure), valid methods of assessing both current and historical sun exposure are needed. While genetic factors probably play some role in melanogenesis, no study has yet managed to distinguish genetic from sun exposure-related risks. We will address both these issues in a case-control study of identical twins (nested in an established population-based cohort of 52,000 twins in California) assessing the role of sun exposure in melanoma etiology in the absence of genetic effects. Historical sun exposure will be assessed by combining residential history with novel fine-layer interpolated solar radiation level using GIS: we have already shown this method significantly reduces misclassification and recall bias. We will measure the actual impact of solar radiation on the skin, measuring UV- induced epidermal damage in tumor specimens noting differences in risk with varying UV intensity and wavelength. These results have the potential to improve primary prevention of melanoma and other skin cancers, and to direct the research team's future work on gene-environment interactions relevant to melanogenesis. We will measure the actual impact of solar radiation on the skin, measuring ultra-violet (UV)-induced epidermal damage in tumor specimens noting differences in risk with varying UV intensity and wavelength, and estimating the risk of melanoma with lifetime and age- specific exposures to specific wavelengths of UV. These results have the potential to improve primary prevention of melanoma and other skin cancers by indicating the appropriate means of avoiding harmful UV exposure, and to direct the research team's future work on gene-environment interactions relevant to melanogenesis.