Skin cancer phenotype

Generally, the phenotype that predisposes an individual to an increased risk of skin cancer is red or blond hair, blue eyes, and fair skin. These characteristics are surrogate measure of the sensitivity of the skin to sun exposure and the tendency to develop nevi, freckles, and sunburns based on the skin type. Freckles, which may appear abruptly after the first high dose of UV radiation sun exposure, represent clones of mutated melanocytes, and their presence is associated with an increased risk of melanoma.12 The Fitzpatrick classification of skin type is used to determine the response pattern of the skin to UV radiation and assess the risk for melanoma. There are six Fitzpatrick skin types Type I skin always burns and never tans, type II skin burns easily and tans rarely, type III skin burns sometimes and tans usually, type IV skin burns rarely and always tans, type V skin always tans and is moderately pigmented (brown), and type VI skin always tans and is darkly pigmented (black). Fitzpatrick I and II skin types are commonly affected by NMSC and MM. The susceptibility to skin cancer, both NMSC and MM, is related to the melanin content of the skin and the skin s response to UV radiation. 

It is also clear that apart from exposure to carcinogens, other factors such as the genetic predisposition of the organism exposed may also be important. Thus, patients with the genetic disease xeroderma pigmentosum are more susceptible to skin cancer. It has already been mentioned that the incidence of bladder cancer is significantly higher in those individuals who have the slow acetylator phenotype. 

Although the link between skin cancer and exposure to sunlight is very strong, the susceptibility of individuals to the carcinogenic effect of UV radiation varies depending on several factors including skin pigmentation, age, sex, and phenotype. Particularly, factors such as fair skin, blue eyes, red or fair hair, and inability to tan have been linked to increased risk of NMSC in several studies (270-276). 

By contrast, deficiencies in GG-NER (see Section 11.3) lead to the inherited disorder xeroderma pigmentosum (XP), which can be viewed as the prototypical DNA repair disorder [7-9]. XP patients are unable to repair UV lesions, and as a consequence suffer from an extreme sensitivity to UV light and an over 1000-fold increased incidence of skin cancer. Severely affected XP patients additionally suffer from neurological abnormalities. The phenotypes of two additional symptoms associated with NER genes, Cockayne syndrome (CS) and trichothiodystro-phy (TTD), are more complex as they are due to defects in transcription as well as defects in DNA repair [10]. 

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