DIVERGENT CAUSAL PATHWAYS TO MELANOMA: A COMBINED ANALYSIS OF 12 CASE-CONTROL STU - DESCRIPTION (provided by applicant): Melanomas are common cancers arising from the pigment cells of the skin. Each year, more than 62,000 people are diagnosed with invasive melanoma in the United States, resulting in almost 8,000 deaths annually. Sunlight is the principal factor that causes melanoma, although there is increasing evidence that the role of sunlight in causing melanoma is not the same for all people. We have recently proposed a "divergent pathway" hypothesis for the development of melanoma. Under this model, we posit that people who are prone to develop nevi (moles) are at higher-than-average risk for melanoma. We hypothesize that such people will develop melanoma after modest amounts of sun exposure, and will do so on body sites with large populations of pigment cells such as the back. In contrast, other people who are less prone to developing nevi require exposure to large cumulative doses of sunlight to develop melanoma, and these melanomas will tend to arise on habitually sun-exposed body sites such as the head and neck. Epidemiologic and molecular evidence in support of this hypothesis has been published based on analyses of small datasets. This new project aims to test the divergent pathway hypothesis for the development of melanoma by undertaking a systematic re-analysis of the original study data collected from 12 case-control studies comprising individual data records for 2,954 people with melanoma and 3,685 healthy controls. The primary objective is to compare patients with melanomas arising at different body sites (trunk, head & neck, upper limb, lower limb) with melanoma- free controls to determine whether the distribution of nevi and sun exposure differs among the groups. When complete, this study will provide new information about the causes of melanoma. Such knowledge is crucial to controlling and preventing this cancer. Melanomas are common cancers of the skin caused by sunlight. This project aims to find whether melanomas at different body sites arise through different combinations of causal factors. Ultimately, the results of this research may contribute to better preventive strategies to reduce the number of people who die from melanoma (currently 8000 people each year in the United States).
