Ultraviolet Radiation and Sunlight
The main cause of melanoma and other skin cancers is exposure to UV radiation from the sun and other sources, such as tanning machines in solariums. Overall, exposure to ultraviolet (referred to as UVA or UVB) radiation from sunlight accounts for about 90% of the symptoms of premature skin aging and most of these effects occur by the age of 20.

Melanoma occurs more often in people who are exposed to the sun every now and then, that is, on weekends or on holidays, rather than a little bit everyday. However, people who receive a lot of sun exposure, in a more continuous pattern, are also at increased risk.

Melanoma is more likely to be caused by intense exposure to sunlight in early life.

Each time your unprotected skin is exposed to UV radiation, it changes the structure of the cells and what they do. Overexposure to UV radiation permanently damages the skin and the damage worsens with more UV radiation.

UVA and UVB Radiation.
When sunlight penetrates the top layers of the skin, ultraviolet radiation (referred to as UVA or UVB) bombards the genetic material, the DNA, inside the skin cells and damages it.

UVB radiation is the primary cause of sunburn and mainly affects the skin’s outer layers. UVB is most intense at midday when sunlight is brightest. It is interesting to note that slightly more than 70% of the yearly UVB dose is received during summer and only 28% is received during the remainder of the year.

On the other hand, UVA radiation penetrates more deeply and efficiently, however, UVA's intensity also tends to be less variable both during the day and throughout the year than UVB's. For example, only about half of the yearly UVA dose is received during the summer months and the balance is spread over the rest of the year. UVA is also not filtered through window glass (as is UVB).

Damaging Effects of UV Radiation.

Both UVA and UVB rays damage the skin, including genetic injury, wrinkles, lower immunity against infection, aging skin disorders and cancer, although the reasons for this are not yet fully understood. The following are some ways in which cancer may develop and some defensive actions that the skin uses to protect itself against DNA damage.

• Oxidation and Antioxidants. UV radiation affects the production of oxidants, also called free radicals. These free radicals are unstable molecules produced by normal chemical processes in the body that, in excess, can damage the body's cells and even alter their genetic material, contributing to the aging process and sometimes to cancer. The large surface area of the skin makes this organ a prime target for oxidants.

• Defective DNA Repair and Protective Enzymes. Some melanomas and other skin cancers are caused by a breakdown in the mechanisms that help repair DNA damage. This can occur due to various causes including an inherited condition called xeroderma pigmentosum (XP). A number of enzymes in the skin help protect against this damage. One repair enzyme called T4 endonuclease 5 (T4N5) is, in fact, being investigated in lotions to protect against skin cancers.

• Breakdown of Immune Protection. Specific immune factors protect the skin, including white blood cells called T lymphocytes and specialized skin cells called Langerhans cells. These immune factors attack developing cancer cells at the earliest stages. Unfortunately, certain substances in the skin, in particular a chemical called urocanic acid, suppresses these immune factors when exposed to sunlight, setting the stage for skin cancers.

Defective Cell Death (Apoptosis). Apoptosis is the last defense of the immune system. It is a natural process of cell-suicide, which occurs when cells are severely damaged. Apoptosis in the skin kills off cells harmed by UVA preventing them from becoming cancerous. (The peeling after sunburn is the result of these dead skin cells.) In some cases, however, genetic mutations or other factors derail apoptosis. If this occurs, the cells can become immortal and continue to proliferate, resulting in skin cancers.

Genetic Factors
A number of genetic factors are being investigated for their role in melanomas, including inherited genes and genetic defects that are acquired from environmental causes (particularly sunlight).

Mutations in Genes that Regulate Cell Growth.
Non-inherited mutations in a number of genes that inhibit tumor growth or other cell-protecting properties may account for cancerous changes in moles and for aggressive melanomas. The following are some examples.

• Important studies have now identified a mutation in the BRAF gene that appears to be the most common event in the process that leads to melanoma. Some researchers have observed mutations in 66% of malignant melanomas. Researchers hope that agents that block this gene may provide a viable treatment option.

• P16 is a tumor suppressive gene that may be abnormal in some melanoma cases.

• CDKN2A Mutations. Mutations in a genetic regulator called CDKN2A are the most common causes of inherited melanoma (which accounts for only a small proportion of melanoma patients). Mutations in this gene also appear in non-inherited cases of melanoma. Genetic tests are being developed for CDKN2A.

Abstracted from MD Consult Patient Information Material

How does melanoma develop

Like cancers in other parts of the body, melanomas are composed of cells which multiply without the normal control of the body's regulating systems. Just as the specific cause of most cancers is not fully understood, it has not yet been possible to completely identify how melanoma develops. It has been established, however, that people living in climates with high levels of ultraviolet light have an increased risk of melanoma. It appears that the ultraviolet (ionizing) radiation may directly mutate (corrupt) segments of the genetic code located in melanocyte chromosomes which is responsible for cell control.

Nonetheless melanoma does not always occur in body parts which have received the most sunlight exposure. It is important to understand that cancers do not develop directly from normal cells but progressively evolve in a series of stages that can frequently be easily identified by expert examination. A number of changes in the skin can be identified as representing changes in the pigment cells which are pre-cancerous.