Malignant melanoma is a type of skin cancer that results from melanocytes, the cells that produce pigments in the skin. It can spread to other body parts if not detected and treated early. Prevention includes sun protection measures, and treatment may include surgery, immunotherapy, or targeted therapy, depending on the cancer stage. The assessment of the Polygenic Risk Score for malignant melanoma is based on the examination of 60 gene polymorphisms.
Genetic testing for malignant melanoma is included along with 12 other diseases in the Genetic Screening for Sensory Organs and Skin Diseases, Polygenic Risk Score, as well as in the Genetic Screening for Neoplasms and Precancerous Malformations, Polygenic Risk Score, along with 19 other diseases.
Causes and non-genetic risk factors
Skin cells develop in a controlled and orderly manner. The new cells push the old ones to the skin surface, where they die and are eliminated from the body. When some cells acquire DNA damage, uncontrolled growth of new cells can be triggered, resulting in skin cancer. Most of the time, the genetic changes associated with melanoma are acquired during life and are not passed on (not inherited). In some cases, they occur randomly in a cell, with no apparent cause; in others, they are likely to occur due to an external cause. It is therefore likely that a combination of environmental and genetic factors leads to the development of melanoma. Ultraviolet (UV) rays, especially type B and type A, are a significant cause of melanoma as they can damage the DNA of skin cells. However, UV light does not cause all melanomas, especially those that occur on body parts not exposed to sunlight so that other factors can influence the risk of melanoma.
The following factors can increase a person's risk of developing melanoma:
- Sun exposure: Living at high altitudes or in areas with intense sunlight year-round are at increased risk, as well as staying outdoors during extended midday periods
- Indoor tanning in sunbeds, tanning salons, or sunlamps. Their use is strongly discouraged
- Moles: People with many moles or unusual, large moles with irregular shape and color (dysplastic nevi or atypical moles) are at increased risk
- Fair skin: People with fair complexion, blond or colored hair, blue eyes, and freckles have a higher risk of developing melanoma. This risk is also higher in people who tend to burn their skin rather than tan
- Previous skin cancer. People who have already had melanoma or basal cell or squamous cell skin cancer have a higher risk of developing melanoma
- Ethnicity: While it can develop in individuals of any ethnicity, people of Caucasian descent are 20 times more at risk than those of African descent
- Age: It occurs in young adults more frequently than many other cancers. The median age of diagnosis is around 50 years
- Weakened immune system: Both disease and immunosuppressive treatments increase the risk of developing skin cancer, including melanoma
Additionally, and less frequently, it is possible to inherit genetic changes from parents that increase the risk of melanoma. About 10% of people with melanoma have a family history of the disease. The risk of developing melanoma is 2 to 3 times higher than the average risk if there is a close relative affected. This risk increases if several family members living in different places have been diagnosed with melanoma. In addition, hereditary familial forms of melanoma due to changes in specific genes such as CDKN2A, CDK4, P53, and MITF have been described, although rare. Other hereditary conditions (xeroderma pigmentosum, Li-Fraumeni syndrome, or hereditary breast and ovarian cancer, among others) are also associated with an increased risk of melanoma.
Symptoms
Melanomas can form anywhere on the body, although they most frequently appear in areas that have been exposed to the sun (back, legs, arms, or face). They can also occur in areas without sun exposure, such as the soles of the feet, palms of the hands, or nail beds, although this usually occurs in individuals with darker skin.
Changes in the size, shape, color, or texture of a mole are often the first warning signs. These changes can occur on an existing mole or in the form of a new or unusual-looking mole; however, they can also appear on normal-looking skin. In 75-80% of cases, melanoma appears without a previous mole.
The ABCDE rule summarizes the suspicious features of a pigmented skin lesion:
- Asymmetry: The lesion is not rounded
- Borders: The borders are irregular
- Color: The lesion has different non-homogeneous colors
- Diameter: The size of the lesion is more significant than 6 mm
- Evolution: The previous characteristics have presented changes over time
Prevention
Although we are still trying to clarify the causes of melanoma and its prevention, we can act on the known factors to reduce the risk as much as possible. The most important way to reduce the risk of melanoma is to protect yourself from UV exposure:
- Depending on geographic location, limit or avoid direct sun exposure during the central hours of the day, when solar radiation is most intense. Preferably, stay in the shade.
- Wear sun-protective clothing, hats that protect the face, neck, and ears, clothing with a UV protection factor, and sunglasses with UV protection.
- Use plenty of broad-spectrum UVA and UVB sunscreen with a sun protection factor (SPF) of at least 30 over the whole body, even if the day is cloudy, every 2 hours or more frequently when perspiring or bathing.
- Avoid sun lamps or tanning beds and tanning salons.
- Examine the skin regularly, including self-examination, to check for new bumps or changes in existing moles, freckles, bumps, and birthmarks, and have it evaluated by a dermatologist.
