Melanoma Skin Cancer

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Causes, Risk Factors, and Prevention TOPICS

Do we know what causes melanoma skin cancer?

Although researchers have found some things that can raise a person’s risk of melanoma (see “What are the risk factors for melanoma skin cancer?”), it’s not yet clear exactly how these factors cause melanoma.

For example, while most moles never turn into a melanoma, some do. Researchers have found some gene changes inside mole cells that may cause them to become melanoma cells. But it is still not known exactly why some moles become cancerous or why having many moles or atypical (dysplastic) moles increases your risk of developing melanoma.

Researchers have learned a great deal in recent years about how certain changes in DNA can make normal cells become cancerous. DNA is the chemical in each of our cells that makes up our genes – the instructions for how our cells function. We usually look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes control when our cells grow, divide into new cells, and die. Certain genes that help cells grow, divide, and stay alive are called oncogenes. Genes that keep cell growth in check or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Changes in several different genes are usually needed for a cell to become cancerous.

Ultraviolet (UV) rays are clearly a major cause of many melanomas. UV rays can damage the DNA in skin cells. Sometimes this damage affects certain genes that control how skin cells grow and divide. If these genes no longer work properly, the affected cells may form a cancer.

Most UV rays come from sunlight, but some can come from man-made sources such as tanning beds. Usually it’s not clear exactly when UV exposure causes DNA damage that might eventually lead to cancer. Some of the damage may take place in the few years before the start of the cancer. But much of it may be from exposures that happened many years earlier. Children and young adults often get a lot of intense sun exposure that might not result in cancer until many years or even decades later.

Most of the gene changes commonly seen in melanoma cells are not inherited. They are more likely the result of damage caused by sunlight. In some people, such as those with xeroderma pigmentosum (XP), the skin cells are not as able to repair damaged DNA. These people are more likely to develop melanoma.

Some melanomas occur in parts of the body that are rarely exposed to sunlight. These melanomas often have different gene changes than those in melanomas that develop in sun-exposed areas.

When melanomas run in families, gene mutations that greatly increase the risk of melanoma are often passed from one generation to the next. Familial (inherited) melanomas most often have changes in tumor suppressor genes such as CDKN2A (also known as p16) and CDK4 that prevent them from doing their normal job of controlling cell growth. Scientists reason that this could eventually lead to cancer.

Many other gene changes have been found in melanoma cells as well. Some of these have proven to be good targets for drugs to help treat this disease. For example, about half of all melanomas have a change (mutation) in the BRAF oncogene that helps drive their growth. This change is not inherited. It seems to occur during the development of the melanoma. Several drugs that specifically target cells with this gene change are now used to treat these melanomas (see the section “Targeted therapy for melanoma skin cancer”).

Last Medical Review: 03/19/2015
Last Revised: 02/01/2016