Melanoma is a form of cancer that develops from the pigment producing cells of the skin. If untreated it can spread through the body and is potentially fatal.

In many parts of the world melanoma is becoming more common. However, it is still unusual to have more than one case of melanoma in a single family. When more than one person in a family has a melanoma, there might be something ‘running in the family’. That ‘something’ could mean other family members are more likely to get a melanoma than people outside the family.

The following information is for people who suspect that their family carries an increased risk of melanoma. It is also for people who have been told that they have such an increased risk.

Words in bold are defined in the Glossary at the bottom of this page.

There is a detailed CD-Rom/DVD called “Melanoma – Dealing with the diagnosis”. This was produced by Professor Newton Bishop, and colleagues from St James’s University Hospital in Leeds and from Bradford Royal Infirmary. The presentation contains text about melanoma, its diagnosis and treatment.

The information in this booklet is about dealing with melanoma, and is intended for patients who have recently been diagnosed with melanoma, and their families. This booklet contains written information, illustrations and photographs.

To download and view the PDF online version please click here.

The genes that we inherit from our parents can affect our risk of developing certain diseases. Sometimes genes have faults (called mutations) that can increase our chances of developing a disease. Certain mutations in a gene called CDKN2A can increase your chances of developing melanoma. This paper describes how GenoMEL looked at the families within its studies to see what having these CDKN2A mutations can mean. 385 families were involved across Europe, North America and Australia. Each family contained three or more relatives who had previously developed a melanoma.

Of the total number of families studied 39% had CDKN2A mutations. However, the percentage of families with a mutation varied by continent. Only 20% of the families in Australia contained a CDKN2A mutation, whilst in North America and Europe the figure was 45% and 57% respectively.

In comparison with other families it is known that families with a CDKN2A mutation may have:

Melanomas

GenoMEL looked to see if these four features were related to CDKN2A mutations in the 385 families studied. It found that the features were related to the presence of a mutation, although the Australian families did not show an increased risk of pancreatic cancer. Also, the relative importance of these features varied by continent.

The strongest link between having a mutation in this particular gene in the family and having multiple cases, early onset, and so forth, was in Europe followed by North America and then Australia. This is probably explained by the varying rates of melanoma on each continent and the role of the environment. Australia has the highest rate of melanoma of the three continents due to its very sunny climate and its population largely having lightly pigmented skin. Therefore, in comparison to families on the other continents, Australian families with several cases of melanoma were more likely to be due to these factors rather than possessing a CDKN2A mutation.

The way in which our genes, environment and life style interact influences our chances of developing melanoma. This paper adds to our understanding of this interaction, and GenoMEL is continuing its studies to learn more.

The original paper can found at the web site of the Journal of Medical Genetics - http://jmg.bmj.com/cgi/content/full/44/2/99

GenoMEL has collected blood samples to look for genetic changes (mutations) that increase the risk of developing melanoma. We looked at particular genes, called CDKN2A and CDK4, using the samples given for research by melanoma families. GenoMEL also looked to see if having mutations in these genes increased the risk of pancreatic cancer, nervous system tumours or some rare melanomas of the eye (uveal melanoma).

This study included 2,137 participants from 466 families from around the world. These families had at least three people who had developed a melanoma.

Overall, 41% of families in this study had one of these mutations. Most of these mutations were in the CDKN2A gene, affecting a protein called p16. The CDKN2A gene is very unusual in that mutations can also affect another, quite different, protein called ARF. Although mutations affecting the ARF protein were found in some melanoma families, they were rare. Occasionally there are mutations that affect a different gene, called the CDK4 gene, but these were also uncommon.  There were only five mutations in the CDK4 gene and seven mutations in the part of the CDKN2A gene that affects ARF.

There were large differences in the types and numbers of particular mutations found in different geographical areas.

Most families studied had an increased risk of melanoma. Mutations in the CDKN2A gene also increased the risk of pancreatic cancer in some families, but the level of that increase varied.  There was also variation between countries so that there was no definite increased risk of pancreatic cancer in Australian families.

The increased risk of pancreatic cancer is clearly of great concern to families and to GenoMEL, and we are hard at work determining how to predict which families are at increased risk. At the moment, it is not clear whether the increased risk in some families is due to the type of mutation or to interaction with environmental factors.

There did not appear to be an increased risk of uveal melanoma.  The results for nervous system tumours were less clear.  There was a possible relationship between nervous system tumours and mutations altering ARF but more work is needed to understand this relationship.

This GenoMEL study provides the most detailed description of mutations in these particular high-risk genes in families with three or more melanoma cases to date.

The original paper can found at the web site of Cancer Research at: http://cancerres.aacrjournals.org/cgi/content/full/66/20/9818

Page updated: 23/10/07