Non-Melanoma

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There are many causes of skin cancer, although ultraviolet (UV) radiation - especially ultraviolet B (UVB) radiation - is an important "risk factor" that makes people more prone to developing both melanomas and non-melanomas (see Types of Skin Cancer). It is likely that exposure to UV radiation causes changes in the genetic material - the DNA (deoxyribonucleic acid) - within skin cells. Such changes add up over a lifetime and eventually may give rise to skin cancer. In fact, experts suggest that about 90% of all skin cancers are associated with exposure to UV radiation.

To prevent excessive UV exposure, the American Academy of Dermatology (AAD) recommends:

• seeking shade whenever possible;
  
• wearing sun-protective clothing;
  
• using a broad spectrum sunscreen with a Sun Protection Factor (SPF) of 15 or more, and
  
• avoiding the midday sun (from 10:00 am to 4:00 pm) by following the "shadow rule": if your shadow is shorter than you are, the sun's rays are at their strongest and you are more prone to sunburn.

The Skin Cancer Foundation has classified skin types into six subgroups according to the person's inclination to sunburn:

• Type I: always burns, never tans, and is very fair-skinned (red or blond hair, freckles)
  
• Type II: easily burns, tans minimally, and usually is fair-skinned
  
• Type III: occasionally burns, gradually tans
  
• Type IV: minimally burns, always tans
  
• Type V: very seldom burns, always tans, and has medium-to-heavy pigmentation (skin coloration)
  
• Type VI: never burns, tans darkly, and has heavy pigmentation (e.g., African Americans and other racial groups)

Non-Melanoma Skin Cancer
The following are some of the most notable risk factors for the development of basal cell and squamous cell carcinomas:

• Fair Skin
  Like individuals with melanoma, the people who are at greatest risk of developing basal cell or squamous cell skin cancers are fair-skinned whites with blond, red, or light brown hair and blue, green, or gray eyes. Such individuals always sunburn, never tan, and freckle easily.
  
  Ultraviolet B (UVB) Radiation Exposure. The risk of non-melanoma skin cancer is increased among people who have histories of
  • blistering sunburns during childhood;
  • outdoor occupations;
  • outdoor hobbies or sports interests (skiing, hiking, jogging, etc.);
  • homes in very sunny climates;
  • "weekend tanning" habits; or
  • frequent use of tanning lamps or booths.

  The risk of non-melanoma skin cancer is about twice as high in areas with year-round, bright sunlight (e.g., Arizona) as it is in places that are more overcast in climate (e.g., Minnesota).

• Gender
  In comparison to women, men have a two-fold higher risk of developing basal cell carcinoma and a three-fold higher risk of developing squamous cell carcinoma of the skin.
• Occupational Exposure
  Workers may have an increased risk of non-melanoma skin cancer if they have had contact with industrial chemicals such as arsenic (a heavy metal used in the manufacture of some pesticides), or hydrocarbons found in coal tars, chimney soot, pitch, paraffin, asphalt, and some oils.
• Previous Skin Injury
  Non-melanoma skin cancers are more likely to arise from skin that has
  • scars due to severe burns, vaccinations, or even tattoos;
  • grave damage from previous skin disease or inflammation (e.g., long- standing skin ulcers); or
  • covered regions of extreme bone infections.
• Medical Therapies
  Certain skin conditions, such as psoriasis, are treated with therapies such as psoralen plus ultraviolet light ("PUVA"). Psoralen is a drug that can make cells light sensitive. It is taken orally, and then the patient's skin is exposed to ultraviolet radiation. Such exposure can increase the person's risk of developing squamous cell and other skin cancers.
• Radiotherapy
  Radiation therapy for cancer and other diseases results in a higher risk of skin cancer in the general vicinity of exposure during treatment.
• Immune Suppression
  It appears that there may be a relationship between the status of a person's immune system and the development of skin cancer, but this relationship is not well understood. People with suppressed immune systems - such as organ transplant recipients - are more likely to develop skin cancers. Squamous cell carcinoma, in particular, represents a real threat to transplant patients. This type of skin cancer can be very aggressive and metastasize (spread) to other tissues of organs) in immunosuppressed patients.
• Family History/Genetic Factors
  Certain individuals may have an inherited, "genetic" predisposition towards the development of skin cancer. There are several inherited disorders that may lead to a higher risk of skin cancer. These include:
  • Xeroderma pigmentosum (XP) - This is a rare, inherited disease that is caused by a defect in an enzyme that repairs damage to DNA (deoxyribonucleic acid, the chemical that encodes the genes). People with XP are photosensitive and less able to repair DNA damage caused by UV radiation. They are prone to developing numerous skin cancers on areas of their bodies that have been exposed to sunlight. XP occurs in 1 out of every 250,000 individuals within the United States and in 1 out of every 40,000 people in Japan.
  • Nevoid Basal Cell Carcinoma Syndrome (NBCCS) - Also known as Gorlin-Goltz syndrome or Gorlin syndrome, this syndrome is an inherited condition that is characterized by basal cell carcinomas (BCCs) of the skin; "pitting" of the palms of the hands and soles of the feet; and abnormalities in the jaws (e.g., cysts), bones (e.g., calcium deposits within the skull, cleft lip or palate), eyes (strabismus, or crossed eyes), and the central nervous system. NBCCS - which is associated with a single mutation in a tumor suppressor gene - increases the risk of developing other tumors, such as medulloblastoma (a brain cancer), meningioma (a vascular tumor of the central nervous system), and ovarian fibromas (fibrous connective tissue tumors of the ovaries).

The treatment of the basal cell carcinomas in these individuals should not include radiotherapy (radiation therapy, e.g., with x-rays), as it may lead to the development of additional basal cell carcinomas. Instead, photodynamic therapy with agents such as tin ethyl etiopurpurin (SnET2) may prove beneficial.

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