MECHANISMS OF INDUCTION OF SKIN CANCER BY UV RADIATION

Holly Soehnge, Allal Ouhtit and Honnavara N. Ananthaswamy

Department of Immunology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd., Box 178, Houston, TX 77030

Received 10/20/97 Accepted 10/24/97

2. INTRODUCTION

The incidence of skin cancer has been increasing at an alarming rate over the past several decades; it is estimated that over one million new cases of non-melanoma skin cancer (NMSC) occur each year in the United States (1). Mortality from NMSC is low, but there is a considerable morbidity with regard to disfigurement and medical costs; the estimated cost per year for treatment of NMSC is over $500 million (2). The incidence of skin cancer is expected to rise further, emphasizing the importance of increased prevention and treatment efforts.

The relevance of sunlight exposure to the skin cancer epidemic is well known. Increased recreational exposure to the sun has been a major contributory factor in the rising skin cancer incidence (1, 2). The incidence of NMSC increases in proportion to cumulative sunlight exposure, such as in those who work outdoors, and in the elderly (1). The skin responds to sun exposure by tanning and skin thickening, which provides some protection from further damage by the ultraviolet radiation. The degree of pigmentation in the skin and the ability to tan are important factors in the risk of development of skin cancer; the risk of NMSC is highest in people who sunburn easily and suntan poorly, with the least degree of protective skin pigmentation (1). Rising concerns over the depletion of the ozone layer due to human influences, particularly the use of chlorofluorocarbons, has increased the awareness of the dangers of sun exposure and has spurred much research into the ways in which the UV radiation in sunlight causes skin cancer to develop.

UV radiation has mainly been implicated in the development of non-melanoma types of skin cancer. Although the relationship between sun exposure and the incidence of melanoma is not clear, some epidemiological evidence suggests that UV exposure does influence the development of malignant melanoma (1). UV radiation induces cancer in the skin through damaging the ability of skin cells to control cell proliferation; the cell has mechanisms to counteract this damage before cancer can develop, including DNA repair, apoptosis, and immune surveillance. UV radiation can damage skin cells by forming dimers in DNA between adjacent pyrimidine residues, potentially leading to UV "signature" mutations that can accumulate over time (3, 4). The cell can respond to the damage by repairing the DNA to avoid harmful mutations, or if the damage is too great, by inducing apoptosis to remove potential cancer cells from the population (4). Failure of these pathways can result in the loss of control of cell proliferation and allow a skin tumor to develop, through the inactivation of tumor suppressor genes or the activation of oncogenes. The importance of DNA repair mechanisms in the prevention of skin cancer is evident from the high incidence of skin cancer in patients with diseases that affect such processes, such as xeroderma pigmentosum (XP) (2). Immune surveillance in the skin also plays an important role in protection against the development of skin cancer. UV exposure acts to depress the function of the immune system in the skin, creating a more favorable environment for the development and growth of tumors (reviewed in ref. 5). There has been much research interest in the study of the processes by which skin cancer is induced by UV radiation; the purpose of this article is to provide an overview of recent advances in this area.