Skin cancer breakthrough – Gene explains why men are at higher risk of malignant melanoma

Researchers from Germany have identified a gene that is associated with an increased risk of suffering from skin cancer. The research, published this month in Journal of Carcinogenesis, could also explain why men are more likely to suffer from malignant melanoma than women.

Although most people associate melanoma with exposure to UV light, through excessive sunbathing for example, the disease can be inherited – indicating that faulty genes are also partly to blame. Genetic risk factors also affect the likelihood of individuals suffering from non-inherited, or sporadic, melanoma.

To identify these risk factors, researchers from the University Hospital in Tuebingen took blood samples from 450 healthy volunteers, and 500 people who had been diagnosed with malignant melanoma, from which they could extract DNA. In collaboration with Genefinder Technologies Ltd., Munich, Germany and Sequenom Inc., San Diego, USA, the researchers studied the DNA samples, looking for slight differences in the genes between people with melanoma skin cancer and people with no cancers at all. To do this they screened more than 25,000 sites across the whole genome, which are known to vary naturally between different people.

The researchers identified a gene called BRAF that contains several sites of natural variation. Some variants were more likely to be found in people who suffered from melanoma than in those that did not. But, when the data was separated by sex, it appeared that the variants only conferred a higher risk of suffering from melanoma on men who carried them.

At present, men have a 1 in 58 chance, and women a 1 in 82 chance of developing the disease in their lifetime. The researchers write: “BRAF may be one explanation of why males have an increased lifetime incidence of melanoma compared to females”.

Until now, the best-known risk factor for melanoma was if you had a mutated copy of the gene CDKN2A. This gene could explain about 25% of the inherited cases of melanoma, which equates to about 1% of the total number of cases.

The risk associated with BRAF is much more significant. The researchers write: “We estimate that BRAF could account for an attributable risk of developing melanoma of approximately 4% in the German population. This risk estimate is much higher than that attributed to CDKN2A.”

Dr Peter Meyer, the managing researcher of this study, said: “It will be exciting to learn more about whether BRAF is also associated with melanoma-risk in other populations with higher melanoma incidences like Australians.”

The BRAF gene encodes a protein that activates the growth and multiplication of cells. Recent studies have shown that mutations in BRAF, which cause the protein to become more active, are commonly found in melanomas and moles. The variants that have been identified in this study do not have any effects on the activity of the protein – how they increase the risk of suffering from melanoma is currently unknown.

Professor Claus Garbe, the principal investigator of the project said: “Moles are a major risk factor for the development of malignant melanoma. BRAF mutations occur in the majority of melanomas but also in moles. We are therefore interested in addressing the question of whether carrying certain variants of the BRAF gene could predispose people to having or developing more moles, and thus to an increased risk of developing melanoma”

Dr Goppala Kovvali, the Editor-in-chief of Journal of Carcinogenesis said: “This article is an important contribution to the field of carcinogenesis. I anticipate that several studies will be undertaken to investigate the BRAF gene in connection with melanoma, especially in the United States and Australia where skin cancer is one of the common cancers.”

The incidence of malignant melanoma has rapidly increased in recent years. It is the leading cause of death from skin disease, as once the cancer has spread it is resistant to most available treatments.