Exploring a New Paradigm in Melanoma Prevention
Abstract
This study is being applied to the Fiscal Year 2015 Peer Reviewed Cancer Research Program Military Relevance Focus Area of Melanoma and Other Skin Cancers. Melanoma is the most aggressive type of skin cancer, and its incidence has been increasing at a steady state over the past decades. The main factor for melanoma development is an excessive exposure to solar ultraviolet radiation (UVR) that causes skin burns. The invisible effect of solar UVR, however, is the generation of DNA damage in skin cells caused by the absorption of its high energy. If the damage is not properly repaired, it will cause mutations that may lead to the malignant transformation of melanocytes (cells that produce melanin) into melanoma. Skin cells have complex machinery that is in charge of repairing the damage caused by UVR. However, in certain circumstances, the amount of damage is such that it surpasses the cells capacity to repair, increasing the chances to developing skin cancer, including melanoma. Skin color is an important determinant of the risk of developing melanoma. Because dark-skinned individuals have a large amount of a protective pigment called eumelanin that shields their DNA, they have a lesser chance of developing melanoma. On the contrary, individuals with fair skin have large amounts of another type of reddish/yellow pigment called pheomelanin that has poor capacity to protect the DNA, which therefore increases their chance of developing melanoma. It has recently been discovered that pheomelanin can also react with free radicals generated after solar exposure, and during this process it becomes chemically unstable and later releases energy that causes even more mutagenic DNA damage. In other words, this discovery implies that individuals with fair skin may not only be less protected from the damaging effects of solar radiation, but may also accumulate more DNA damage that is produced long after the sun exposure has occurred. Scientific Objective: In this study, we formed a team of scientists working in areas of chemistry, biology, pharmacy, and dermatology in order to study the above described phenomenon in human skin. This is an important research to help understanding the reasons why individuals with different skin color show different risks of developing melanoma. Applicability of the Research: Based on what we know now, it is reasonable to believe that removal of free radicals generated in the skin after solar exposure may prevent the formation of the delayed DNA damage and thus reduce the chances of mutations that may lead to melanoma initiation. We will test the effects of a novel antioxidant agent in reducing free radicals and preventing DNA damage. Relevance to Active Duty Members of Military and Family: This study is of general public interest, but results generated in this research may be particularly relevant to individuals that have fair skin. Among the civilian population, individuals whose skin burns easily usually modify their behavior by avoiding excessive solar exposure. Service men and women, however, regardless of their skin phenotype, are more subjected to sun exposure because of their intrinsic activities. According to a report from the Department of Defense, 71% of the total number of enlisted military personnel is composed of Caucasians. Since the United States went to war in Afghanistan in 2001 and Iraq in 2003, about 2.5 million members of the Army, Navy, Marines, Air Force, Coast Guard and related Reserve and National Guard units were deployed to regions of high solar incidence. The true cost of solar UVR exposure is best demonstrated by the increasing rates of melanoma among young adults, as well as its high incidence in individuals older than 60 years of age. The results from this study may have an immediate impact on the current knowledge of melanoma biology and may provide the rationale for the design of future strategies for melanoma prevention. Because we will be testin
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610489
Entities
People
- Ana Luisa Kadekaro
Organizations
- United States Army
- University of Cincinnati