Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable. Skin cancers, which include basal cell carcinoma, squamous cell carcinoma and melanoma, occur more commonly than any other type of cancer. In general, basal cell carcinomas and the most common squamous cell carcinomas are related to chronic sun exposure and are cured by surgical removal. Melanoma is a potentially fatal type of skin cancer that begins in the melanocytes, which are the cells that are responsible for skin color. The incidence rate of melanoma has been climbing steadily since the early 1970s. In 2003, the American Cancer Society estimated 54,200 cases of melanoma with 7,600 deaths related to the disease. Although melanoma can be successfully cured in its early stages, it is the most common fatal form of skin cancer, accounting for more than 79% of all skin cancer–related deaths. The chance of an individual developing cancer depends on both genetic (inherited) and non-genetic (environmental) factors. Non-genetic or environmental factors may include diet, exercise, or exposure to other substances present in our surroundings. An example of an environmental factor that is known to play a role in facilitating the process of healthy cells turning cancerous is the relationship between tobacco smoking and lung cancers. Other cancers have no known environmental correlation but are known to have a genetic predisposition. A genetic predisposition means that a person may be at higher risk for a certain cancer if a family member has that type of cancer. Melanoma results from a combination of environmental factors (exposure to ultraviolet light) and genetic factors.
Heredity or Genetic Factors
Approximately 10% of individuals diagnosed with melanoma have a family history of the disease. The vast majority of these patients have only one or more affected close relatives, which translates to only a small increase in the risk of developing a melanoma. Those at highest risk for developing melanoma are members of rare melanoma-prone families in which there are usually 3 or more affected members in 2 or more generations on the same side of the family. These family members are generally characterized as having multiple melanomas in the setting of dozens or hundred of atypical moles. The risk of developing melanoma in members of melanoma-prone families is estimated to be around 50% by age 50. By studying these families, researchers have discovered that the DNA of certain genes is often damaged in melanoma cells. Forty percent of melanoma-prone families have an alteration in the gene, CDKN2A, which is a gene that is normally involved in regulating normal cell growth. Research is ongoing to further define the role of CDKN2A in the development of melanoma.
Xeroderma Pigmentosum (XP): Xeroderma pigmentosum (XP) is a rare, inherited skin disorder characterized by extreme sensitivity to ultraviolet light. Individuals with XP have a genetic defect that prevents the repair of sun-induced damage to DNA. As a result, individuals with XP have a 1000-times higher risk of developing skin cancer than the general population. Almost half of individuals with XP develop a skin cancer by the age of 8 and the condition shortens life expectancy by over 30 years.
Environmental or Non-Genetic Factors
Although the causes of melanoma are poorly understood, researchers have identified some risk factors that are associated with melanoma.
Moles (Nevi): Most people have moles and most moles are harmless. Generally, moles develop in children and teenagers and increase in size slightly over time to a maximum diameter of 2 mm or so and remain the same size, shape and color for many years. Normal moles are usually evenly colored brown, tan or black spots on the skin that are round or oval and flat or raised. Atypical moles often called “dysplastic nevi” are defined as moles with a diameter of 5 mm or larger, with an irregular shape and variable color. It is not uncommon to have one or several atypical moles over the extremities or truncal regions. However, about 2% of the population is estimated to have Atypical Mole Syndrome (AMS), which is characterized by the presence of large numbers of moles and atypical moles (100 or more) or moles located on unusual sites (ears, scalp, buttocks, or feet). The lifetime risk for developing melanoma in the U.S. population is estimated to be about 1%. Patients with AMS have a slightly increased risk of developing melanoma (6-10%), which is lower than patients who belong to melanoma-prone families. Melanoma can often be recognized by applying the ABCD rule:
- Asymmetry: The mole is asymmetrical.
- Border Irregularity: The mole has ragged edges.
- Color: The mole is not evenly colored. It may have differing shades of tan brown, black, red, blue or white.
- Diameter: The mole is bigger than 6 millimeters, although some melanomas may be smaller.
A biopsy should be performed on any pigmented lesion that undergoes a change in size, shape or color.
Fair skin: Melanoma is more common in individuals who have fair skin and red or blond hair. With their fair complexions, these individuals tend to burn easily, placing them at a higher risk for developing melanoma. In addition, white people have a 20-times higher risk of developing melanoma than black people because they lack the protective effect of dark skin pigment. However, melanoma can develop in individuals with dark skin.
Ultraviolet (UV) Radiation: UV radiation has been recognized as a major environmental risk factor for melanoma. Sunlight and tanning lamps are sources of ultraviolet radiation. In fact, excessive exposure to the ultraviolet rays of the sun may account for two-thirds of all melanoma cases. Melanoma is more common in individuals who live in areas with greater exposure to UV radiation, such as Australia, New Zealand, Hawaii and California. There has been controversy regarding artificial tanning beds and whether the ultraviolet rays from these beds further increases the risk of melanoma. Several studies have suggested that more than 10 hours of exposure to a sunlamp/sun bed increases the risk of melanoma. However, given the delay between exposure and cancer development this is difficult to prove. The bottom line is that there is good data to suggest that exposure to tanning beds may provide exposure to dangerous levels of UV radiation and that over the next several decades there will be a dramatic increase in melanoma cases related to this hazardous agent.
Weakened Immune System: Individuals with weakened immune systems are at an increased risk of developing melanoma. This includes individuals who have been treated with medicines to suppress the immune system following an organ transplant and individuals who have AIDS or certain types of cancers that weaken the immune system.
Severe Sunburns: Individuals who have had one or more severe, blistering sunburn, especially as a child or teenager, are at an increased risk for developing melanoma. The risk of melanoma is greater for individuals who have had occasional but intense UV exposure than for those who have had consistent but lower level UV exposure, even if the overall UV dose is the same. Although sunburns during adult years are damaging, research indicates that 50-80% of the skin’s lifetime sun damage occurs during childhood or adolescence.
History of Melanoma: The risk of developing a second melanoma in a patient who has had a previous melanoma is estimated to be 3-7% or about 0.25% per year lifetime risk.