Causes and Risk Factors
Sunlight/Ultraviolet Light Exposure
Exposure to sunlight/UV light is thought to be a primary risk factor for melanoma and non-melanoma skin cancers (Erb 2008; Etzkorn 2013). The depletion of the ozone layer is predicted to increase this risk; the World Health Organization has estimated that a 10% decrease of ozone level will result in 300 000 more non-melanoma and 4500 melanoma skin cancers every year (Erb 2008). A lifetime of working outdoors was found to nearly triple the risk of squamous cell carcinoma in one study (Sánchez 2013). Intentional exposure to UV radiation carries additional cancer risk; the use of tanning beds is associated with a 1.5-fold increase in the risk of basal cell carcinoma and a 2.5-fold increase in the risk of squamous cell carcinoma, and extended UV therapy for psoriasis (ie, >250 treatments of psoralen [a phototoxic compound] combined with UVA exposure) may increase skin cancer risk more than 10-fold (Firnhaber 2012). Although cumulative exposure to UV irradiation is associated with skin cancer risk, the nature of exposure may also be a factor (Miller 2006). Intensive sun exposure to the point of severe or blistering sunburn in childhood and teen years is a risk factor for both melanoma and basal cell carcinoma, whereas excessive chronic cumulative exposure is a risk factor for squamous cell carcinoma (Jou 2012).
Age and Gender
Melanoma and non-melanoma skin cancers are more common in men than women (Etzkorn 2013; Siegel 2013) and significantly increase in frequency with age (Dunki-Jacobs 2013; Etzkorn 2013).
Lighter hair color is associated with an increased risk of basal cell carcinoma; in a comprehensive review of 29 studies, dark-haired participants had a decreased risk of basal cell carcinoma compared to those with red hair (2-fold increased risk), blond hair (1.4-fold increased risk), or light brown hair (1.3-fold increased risk) (Khalesi 2013).
Skin types can be described by a continuous scale from I (white skin, always burns, never tans) to VI (dark brown/black skin, never burns, tans deeply) (Roberts 2009). Risk of non-melanoma skin cancers increases with lower skin phototype grade (Etzkorn 2013). Fair-skinned individuals and individuals with skin that burns but does not tan have a 2-fold increased risk of basal cell carcinoma compared to darker-skinned individuals (Khalesi 2013).
Genetics and Family History of Skin Cancer
A personal history of skin cancer increases risk of a non-melanoma cancer (Etzkorn 2013). A family history of skin cancer increases risk of squamous cell carcinoma by 6.5-fold (Sánchez 2013), and a history of two or more first-degree relatives with melanoma increases skin cancer risk more than 10-fold (Firnhaber 2012). Inherited mutations/polymorphisms (altered forms) of certain genes involved in cell cycle signaling (MC1R, CDKN2A) have been identified as risk factors for melanoma or non-melanoma skin cancers; mutations of the CDKN2A gene have been thought to account for approximately 20-40% of familial melanoma cases (Hughes-Davies 1998; Pacifico 2007; Carless 2008; Dunki-Jacobs 2013; Cust 2013; Valverde 1996; Jones 1999).
Concurrent Skin Conditions
Squamous cell carcinoma risk is increased in individuals with other dermatological conditions, including actinic conjunctivitis (2.7-fold increased risk), poikiloderma of Civatte (3.3-fold increased risk), facial actinic keratosis (9.3-fold increased risk), or numerous freckles (3.7-fold increased risk) (Sánchez 2013). Freckling is not associated with increased risk of basal cell carcinoma (Khalesi 2013). Individuals with more than 100 nevi (benign, pigmented growths of the skin, commonly called “moles” or “birthmarks”), or at least 5 atypical nevi, are at more than 10 times the risk of skin cancer than the general population (Firnhaber 2012).
Smoking more than 10 cigarettes a day almost tripled squamous cell carcinoma risk in one study (Sánchez 2013).
Suppression of immune function (such as that caused by immunosuppressant drugs) increases skin cancer risk, especially for squamous cell carcinoma (Erb 2008). In one study, researchers found that organ transplant recipients, who are frequently on immunosuppressant drugs, had a 65-fold increased risk of squamous cell carcinoma compared with the general population (Firnhaber 2012).