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Page: Epidemiology and Causes
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Generally, an individual's risk for developing melanoma depends on two groups of factors: intrinsic and environmental. "Intrinsic" factors are generally an individual's family history and inherited genotype, while the most relevant environmental factor is sun exposure.
Epidemiologic studies suggest that exposure to ultraviolet radiation (UVA and UVB) is one of the major contributors to the development of melanoma. UV radiation causes damage to the DNA of cells, which when unrepaired can create mutations in the cell's genes. When the cell divides, these mutations are propagated to new generations of cells. If the mutations occur in oncogenes or tumor suppressor genes, the rate of mitosis in the mutation-bearing cells can become uncontrolled, leading to the formation of a tumor. Occasional extreme sun exposure (resulting in "sunburn") is causally related to melanoma. Those with more chronic long term exposure (outdoor workers) may develop protective mechanisms. Melanoma is most common on the back in men and on legs in women (areas of intermittent sun exposure) and is more common in indoor workers than outdoor workers (in a British study). Other factors are mutations in or total loss of tumor suppressor genes. Use of sunbeds (with deeply penetrating UVA rays) has been linked to the development of skin cancers, including melanoma.
Possible significant elements in determining risk include the intensity and duration of sun exposure, the age at which sun exposure occurs, and the degree of skin pigmentation. Exposure during childhood is a more important risk factor than exposure in adulthood. This is seen in migration studies in Australia where people tend to retain the risk profile of their country of birth if they migrate to Australia as an adult. Individuals with blistering or peeling sunburns (especially in the first twenty years of life) have a significantly greater risk for melanoma.
Fair and red-headed people, persons with multiple atypical nevi or dysplastic nevi and persons born with giant congenital melanocytic nevi are at increased risk.
A family history of melanoma greatly increases a person's risk because mutations in CDKN2A, CDK4 and several other genes have been found in melanoma-prone families. Patients with a history of one melanoma are at increased risk of developing a second primary tumour.
The incidence of melanoma has increased in the recent years, but it is not clear to what extent changes in behavior, in the environment, or in early detection are involved.
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