When one asks what causes melanoma, the answer is that the question is still under investigation.

There are a number of risk factors for melanoma, and in any one person, one risk factor may be more prominent than others. In another person, no one risk factor may be apparent. Some investigators believe that, in most people, the risk factors for melanoma have a complex inter-relationship that makes it difficult to identify any single factor as the "cause" of melanoma in any individual. Exceptions may be persons with hereditary conditions that strongly predispose to melanoma. (For example: Approximately one-third of non-familial melanomas develop in association with an atypical mole. Atypical moles are found at a much higher rate in first-degree blood relatives of persons with atypical moles, compared to families of individuals without atypical moles.)

Expanding on the discussion of risk factors at the beginning of this section on "Who Is at Risk", we can look in more detail at host (personal) and environmental factors. We will outline them first, then discuss them in detail.

• Genetic or familial risk factors are often associated with a family history of close relatives who had melanoma, large numbers of moles, or dysplastic nevi.
• Skin pigmentation, including skin color (in general, white skin has elevated risk), sensitivity to ultraviolet radiation (tendency to burn rather than tan with initial and repeated exposure to sunlight), and tendency to form freckles and pigmented moles (risk for melanoma appears to be associated with the total number of pigmented moles on a person’s body, and the number of moles larger than a particular diameter).
• Immune deficiency due to a disease such as AIDS or lymphoma, or to immunosuppression after organ transplantation, is associated with a 4-fold to 5-fold increased risk for melanoma. The risk is even higher if the individual has one or more atypical moles or has already had melanoma.

• Sunlight, or more specifically certain wavelengths of the ultraviolet radiation in sunlight that can damage the skin, has a strong epidemiologic association with increased melanoma risk.
• Ultraviolet radiation from sunlamps and sunbeds appears to have a low to moderate epidemiologic association with increased melanoma risk. Some investigators believe that studies of ultraviolet risk often do not sufficiently discriminate between outdoor and indoor ultraviolet exposure of study subjects.

The complexity of inter-relationships between host and environmental risk factors make it difficult to design studies that definitively identify interaction between risk factors as a cause of melanoma. The association between inter-related risk factors and melanoma is often strong (for example, white skin, tendency to freckle, and intense exposure to ultraviolet radiation), but a strong association is not necessarily a "cause".

Nevertheless, a strong association of host risk factors such as white skin and freckling and the environmental risk factor of intense exposure to ultraviolet radiation, is an indication to take preventive measures and regularly self-examine for early signs of melanoma (also look in Self Examination and Prevention). Environmental factors are often more important if associated with a personal history of atypical moles, or a personal or family history of melanoma.

Now, let’s look in more detail at host and environmental factors and their interactions.

Between 5 and 10 percent of people who develop melanoma have a family history of melanoma in a close member of the family. A common pattern of familial melanoma is melanoma in a parent and son or daughter. Melanoma may also have occurred in a grandparent, or brothers or sisters of a parent.

More than a single gene seems to be involved in familial melanoma, so inheritance of a tendency to develop melanoma is more complex than a single "melanoma gene". The genetics of melanoma is the subject of vigorous investigation. A history of melanoma in first-degree blood relatives (e.g., a parent, child or sibling) confers an 8-fold increased risk for developing melanoma. Persons with this history and level of risk should self-examine regularly and be examined by a dermatologist at least every 12 months. Suspicious lesions may be surgically removed and examined under the microscope for changes suggesting malignancy.

Dysplastic nevi are especially important in familial melanoma. Between 2% and 4% of white adults may have at least one dysplastic nevus; the occurrence of dysplastic nevi in black African-Americans and Asians is much less. The risk for malignant change in a dysplastic nevus is significant. Clinical criteria for classifying a nevus as dysplastic include poorly defined borders, irregular pigmentation, or a fried-egg pattern. Lesions are usually 5 millimeters in diameter or larger, but may be smaller. A person with diagnosed dysplastic nevi should regularly self-examine and be examined by a dermatologist every 6 months. 

Certain hereditary conditions such as the extremely rare xeroderma pigmentosum are associated with a markedly increased risk for melanoma. Xeroderma pigmentosum is a genetic disease characterized by ultraviolet light sensitivity, inability to repair ultraviolet-B induced DNA damage, and increased risk for epithelial skin cancer and melanoma.

Skin Pigmentation

The color of your skin can also be regarded as an inherited risk factor. White skin, fair hair, blue, green or gray eyes, sensitivity to ultraviolet radiation (relative inability to tan), and tendency to freckle or form pigmented moles are host factors associated with increased risk for melanoma. A characteristic pattern of freckling is seen in this photo:

The inter-relationship between skin pigmentation and the environmental risk factor of ultraviolet radiation is complex.

Congenital moles (moles present at birth) multiple acquired moles (moles that appear later in life), or one or more atypical moles are known host risk factors. About 3% to 8% of melanomas develop in a congenital mole, and another third of melanomas develop in a dysplastic mole.

The tendency to have numerous moles has a familial association—that is, a person with numerous moles is likely to have a parent, sibling or child with numerous moles.

Here is an important point to remember: Acquired nevi may develop in areas seldom exposed to direct sunlight—such as the buttocks or inside of the thighs—and these also carry of risk for developing melanoma or may be markers for melanoma risk. An acquired nevus does not necessarily have to be exposed to ultraviolet radiation to undergo malignant change. Approximately 40% of 3-year-old children have at least one acquired mole. About 90% of white adults and 70% of non-white adults have one or more acquired moles.

In the case of congenital nevi (nevi present from birth), the size of the mole appears to be an important risk factor for melanoma. However, even small congenital nevi have a significant melanoma risk. Moles known as giant congenital nevi have substantial risk for malignant change—about 15% over a lifetime. A giant congenital nevus is shown in this photo:

Melanoma has been observed to occur more frequently in patients whose immune system has been rendered deficient by disease or by post-transplantation drugs. Diseases that suppress the immune system (and may have an increased risk for melanoma) include AIDS and some lymphomas. Immunosuppressive drugs that are given to retard or prevent organ rejection after transplantation have been associated with an increased incidence of melanoma in transplant patients. Suppression of the immune system limits the body’s ability to immunologically recognize cancer cells, and eliminate them.

In a 1992 monograph, the International Agency for Research on Cancer (IARC) said it found sufficient evidence to state with confidence that solar radiation causes melanoma and other skin cancers in humans. Much of the evidence is epidemiologic—studies of large population groups. Some of the evidence is microscopic interpretation of tissue, linking ultraviolet radiation with damage to skin cells. Ultraviolet wavelengths are the part of solar radiation that is associated with skin cancers.

Solar radiation alone if probably insufficient to cause melanoma. The environmental risk of ultraviolet radiation of varying duration, frequency and intensity interacts with host factors such as genetic predisposition to melanoma, skin pigmentation, tendency to freckle, number and size of moles, and the presence of atypical moles.

A dark-skinned person with no predisposing family history is at substantially less risk for melanoma than a white-skinned, fair-haired person who sunburns and freckles when exposed to intense sunlight.

Epidemiologic studies of exposure to sunlight have shown results that are sometimes difficult to interpret. For example, most studies have indicated that outdoor workers who are exposed to sunlight on a daily basis are at less risk for melanoma than indoor workers. Results such as this require more investigation. In one subtype of melanoma—lentigo maligna melanoma (LMM)—there is a clear association between accumulative lifetime exposure to solar radiation and melanoma risk. LMM is consistently found on chronically sun-exposed parts of the face and body in elderly white-skinned people. LMM accounts for approximately 5% of melanomas in the United States.

The melanoma risk associated with non-solar ultraviolet radiation—e.g., sunbeds and tanning parlors—is not well defined. Some studies have shown slight to moderate increase in risk. Some criticism of the studies points out that it is difficult to differentiate between solar exposure and sunlamp exposure in persons who use both methods to achieve tanning. No evidence has been found to support claims that tanning under sunlamps protects against melanoma.

No chemical or occupational carcinogen has been shown to be a risk factor for melanoma. Studies that indicate some increased risk in certain chemical industry occupations have not been able to separate recreational sun exposure and other melanoma risk factors from occupational exposure to suspected chemicals.

Melanoma risk is usually a complex inter-relationship between host and environmental risk factors. Host factors for skin pigmentation may have a predisposing effect when the person is exposed to certain environmental factors such as intense or long-duration solar radiation. Ultraviolet radiation may result in increased numbers of acquired pigmented moles, and may induce atypical moles to develop melanoma. Ultraviolet radiation can not be held responsible for melanoma in sun-protected sites. The majority of melanomas occur in areas of the body that are regularly covered by clothing.