DESCRIPTION: The incidence of cutaneous melanoma (CM) is increasing faster than any other cancer in the United States. Ultraviolet (UV) radiation is the major environmental etiologic risk factor implicated in the development of CM. However, other environmental agents may also be important. Prior studies have reported associations between arsenic and non-melanoma skin cancers. Our recent study of CM cases and arsenic found an adjusted odds ratio of 2.1 for the highest quartile of arsenic in toenail samples (trend p-value=0.001). We propose to verify these findings through a stronger study design. We will conduct a population-based case-control study of incident CM cases and arsenic content detected in toenail samples. To eliminate biases of our earlier study, we will a) use newly diagnosed cases rather than prevalent cases, b) use toenails collected within 1-9 months of diagnosis, c) use a non-cancer control group, and d) use neutron activation analysis (NAA), considered the gold standard in trace element analyses. CM cases in Iowa residents will be semi-rapid reported through the Iowa Cancer Registry. Population-based controls will be identified using the Iowa Voter Registration file, which is comparable to the Iowa Census data. We will mail subjects an introductory letter, instructions for the toenail sample collection and small baggie. We will then conduct the survey using computer assisted telephone interviewing (CATI) software in order to collect complex data related to residential histories (water source, sun exposure, and occupations). This format will allow interviewers to collect a residential history and probe for additional information about potential exposures at each residence. We will focus on arsenic detected by NAA in toenail samples from cases and controls. Additionally, we will assess known risk factors for CM in this population (including natural and artificial UV exposure, residential and occupational histories, sun sensitivity factors, family history of skin cancer, and sunscreen use). We will also correlate available data on arsenic levels in current drinking water to arsenic in subjects'toenails. Recording residential histories and relating them to current and historical water sources will allow us to examine the length of the potential arsenic exposure, since drinking water is believed to be the main source of arsenic exposure and may provide evidence of long term exposure. Collecting biomarkers of arsenic exposure along with surveying subjects about known UV factors and their sun sensitivity will allow for the examination of important interactions and potential confounding of the association between arsenic and CM. PUBLIC HEALTH RELEVANCE: Melanoma is a public health concern since the incidence is increasing faster than any other cancer in the United States. While ultraviolet radiation is a widely accepted risk factor for this disease, understanding the possible role arsenic exposure may play in the development of melanoma will allow for a more developed base of knowledge regarding the etiology of melanoma. This knowledge will in turn help identify a group of high risk individuals for public health messages to target.