ARSENIC, UV AND MELANOMA IN A NON-HISPANIC WHITE POPULATION: A PILOT STUDY UNDERWAY

Arsenic is a naturally-occurring compound known for its toxicity and carcinogenicity. The US EPA allowable standard for arsenic in drinking water is 10 µg/L (ppb). Paradoxically, arsenic is currently used clinically as an anti-cancer therapeutic. While ingestion of drinking water containing high concentrations of environmental inorganic arsenic is a known risk factor for non-melanoma skin cancer, a significant positive association between body arsenic (toenail) levels and melanoma skin cancer risk has been shown in a (predominantly) Caucasian population in Iowa. Melanoma incidence and deaths in the U.S. continue to rise with a current annual incidence of 60,000 new cases and 8,000 deaths. We here apply an innovative approach to address arsenic exposure as a modifiable co-carcinogenic risk factor that may interplay with UV to increase the incidence of melanoma. Our hypothesis is that arsenic acts as a co-carcinogen with UV exposure in development of malignant melanoma skin cancer in the human population by both inhibiting repair of UV-induced DNA damage and increasing intramelanocyte oxidative stress. This exploratory study provides a novel in vitro-in vivo approach to directly address the hypothesized mechanism by which arsenic may increase the risk of developing malignant melanoma. DNA damage and repair inhibition of UV damage by arsenic is being determined in primary human melanocytes in vitro; in parallel, the association between arsenic drinking water levels and in vivo DNA repair capacity in melanoma cases and non-melanoma reference subjects is being evaluated controlling for UV exposure and serum vitamin D levels. New Mexico provides a unique opportunity for conduct of this exploratory study since melanoma rates are high in fair-skinned populations and both arsenic and UV levels are relatively high across much of the state. Understanding mechanisms by which arsenic may increase the risk of developing melanoma and the range of drinking water exposure concentrations at which these events may occur would greatly improve development of coherent public health prevention strategies.