Overview Of Moles
Moles are growths on the skin. They happen when pigment cells in the skin, called melanocytes, grow in clusters. Moles are very common. Most people have between 10 and 40. A person may develop new growths from time to time, usually until about age 40. In older people, they tend to fade away.
Moles are usually pink, tan, or brown. They can be flat or raised. They are usually round or oval and no larger than a pencil eraser.
About one out of every ten people has at least one unusual (or atypical) mole that looks different from an ordinary one. They are called dysplastic nevi. They may be more likely than ordinary moles to develop into melanoma, a type of skin cancer. You should have a health care professional check your growths if they look unusual, grow larger, change in color or outline, or in any other way.
Are They Determined By Genetics?
Moles are very common, especially in people with fair skin. These overgrowths of skin cells are called melanocytes, but the genetic factors involved in their development are not well understood. Although moles, like tumors, are an overgrowth of cells, they are almost always noncancerous (benign). Perhaps because most are benign, scientists have not studied them extensively, and not much is known about their genetics. Similar numbers of moles seem to occur on individuals of different generations of a family, so a tendency to develop them seems to be inherited, but the inheritance pattern is not well understood.
Most moles occur on parts of the body that are exposed to the sun (ultraviolet radiation), and the number an individual has may increase after an extended time in the sun. They usually begin to occur in childhood. These moles are called acquired melanocytic nevi (and include the subtype epidermal nevus). It is common for new moles to appear during times when hormone levels change, such as adolescence and pregnancy. During an individual’s lifetime, the growths may change in appearance; hair may grow out of them, and they can change in size and shape, darken, fade, or disappear. Infants and the elderly tend to have the fewest.
Sometimes moles are present at birth or develop during infancy. These growths, which are called congenital nevi, are almost always benign. Rarely, a very large growth, called a giant congenital melanocytic nevus, is present at birth. In rare cases, the most serious type of skin cancer (called melanoma) may develop in this type of mole. Large, irregularly shaped, and colored moles called dysplastic nevi or atypical moles can occur at any age. Although not common, they tend to be numerous, and they increase a person’s risk of melanoma. Heredity contributes to the development of dysplastic nevi and to having a higher-than-average number of benign moles. Spending a lot of time in the sun can also increase the number of moles a person has. However, they are often found on areas of the body that are not exposed, which suggests that factors other than ultraviolet radiation from the sun, perhaps hormones or other biologic processes, are involved in triggering the development of acquired melanocytic nevi and dysplastic nevi.
Although the genetics of melanoma has been widely studied, much less is known about genes involved in the development of benign moles. Variations in several genes, including FGFR3, PIK3CA, HRAS, and BRAF, are involved with benign moles. The most studied of these is the BRAF gene. A mutation in BRAF leads to the production of an altered protein that causes melanocytes to aggregate into moles. This altered protein also triggers the production of a tumor-suppressor protein called p15 that stops them from growing too big. In rare cases, BRAF gene mutations together with the deletion of the CDKN2A gene cause a lack of p15, which creates the potential for mole cells to grow uncontrollably and become cancerous (malignant). The formation of cancer is increasingly likely when combined with environmental factors, such as cell damage caused by ultraviolet radiation exposure.
In susceptible individuals (those with fair skin, light hair, skin that burns instead of tans, a family history of melanoma, and genetic risk factors such as deletion of or mutations in the CDKN2A gene), ultraviolet radiation from repeated sun exposure can damage existing moles, increasing their risk of becoming malignant. Research has shown that individuals who have an abundance of moles are at an increased risk of melanoma. However, some people who are diagnosed with melanoma have few moles, and melanoma often develops in areas of the body that are not exposed to the sun. Researchers are working to identify additional susceptibility genes to better understand the genetics and their relationship with cancer.
