Chronic stress and susceptibility to skin cancer

Stress and sunlight and are two factors that affect many people’s daily lives. Both can be beneficial in moderation, but long-term exposure to either can be detrimental in that both may contribute to the development and/or exacerbation of disease. It is estimated that over 2–3 million new cases of non-melanoma skin cancer occur each year (1). Due to a host of psycho-socio-political factors, stress has become an increasing and inevitable part of people’s lives. Chronic stress has been shown to dysregulate immune function (2) and is thought to play a role in the etiology of many diseases. Given the increasing prevalence of exposure to chronic stress and UV and their ability to independently induce pathologic effects, it becomes important to understand whether and how these factors may act together to increase susceptibility to disease. Stress is defined as a constellation of events—a stimulus (stressor) that precipitates a reaction in the brain (stress perception) and activates physiologic fight/flight systems in the body (stress response) (3,4). Chronic stress, defined as stress that persists for several hours a day for weeks, months, or years (3,4), has been shown to have immunosuppressive effects (2) that include suppression of skin cell mediated immunity (3). The ultraviolet B (UVB) component of sunlight is a complete carcinogen and is responsible for most non-melanoma skin cancers (5). Immediate effects of UVB radiation include DNA damage, epidermal hyperplasia and inflammation (6). UVB also suppresses lymphocyte trafficking, T cell, natural killer (NK) cell function (7), and immune responses that are directed against squamous cell carcinoma (8,9). Here we test the hypothesis that chronic stress accelerates the emergence and progression of UVB induced squamous cell carcinoma and inhibits its regression. We examined the effects of moderate chronic stress on the emergence, progression, and regression of squamous cell carcinoma induced by low level (minimal erythemal dose [MED], i.e., without blistering) exposure to UVB radiation in a mouse model. Our goal was to identify potential molecular and cellular immunologic mediators of the exacerbating effects of chronic stress on the emergence and progression of squamous cell carcinoma. Because both squamous cell carcinoma and basal cell carcinoma are immunogenic non-melanoma skin cancers, our findings may also be applicable to basal cell carcinoma, which is the most common form of skin cancer in the United States (10).