Moles, eye colour and the genetics of skin cancer

A gene that is responsible for regulating pigmentation of the skin, and is associated with a greater number of moles and non-blue eye colour, has been linked to a greater risk of melanoma.

The study, conducted by researchers at the Queensland Institute of Medical Research (QIMR), found the variant in the gene MITF significantly increases the risk of melanoma, and could contribute to the high incidence of melanoma in some families.

According to QIMR researcher, Dr Stuart MacGregor, even this small mutation in MITF can significantly increase risk of melanoma, being similar in risk to having red hair.

“This study’s findings are quite alarming, as individuals possessing this genetic variant have a 250 per cent increased risk of developing melanoma, which is as significant to melanoma risk as traits such as having red hair,” Dr MacGregor said.

“This genetic variant showed up more commonly in people that have a family history of melanoma and can be found in approximately 1% of the population. Interestingly, it is more common in those with a higher mole count or with darker eye colour.”

There have been two other genes, CDKN2A and CDK4, that have previously been associated with melanoma risk, both of which account for a small proportion of that risk.

To find this genetic mutation, the researchers conducted a large genome-wide association study (GWAS) on families from Australia and the United Kingdom with a history of melanoma, but which didn’t possess the CDKN2A and CDK4 susceptibility variations. These were compared with controls who had no history of melanoma.

The new gene variant wasn’t common enough to appear in previous GWASs, and there may yet be more rare variants that will emerge from further GWAS studies.

Dr MacGregor said that QIMR is committed to better understanding the genetics of melanoma risk and melanoma development, with a view to improving prevention and treatment of this potentially fatal disease. “Each finding is a step forward in determining accurate risk estimates for melanoma susceptibility and improving the ability to predict those individuals most likely to develop the potentially deadly disease,” Dr MacGregor said.

To carry out this study, QIMR collaborated with the Harvard Medical School; the Westmead Millennium Institute for Medical Research; the University of Sydney; the University of Melbourne; the Melanoma Institute Australia; Leeds University and the Translational Genomics Institute, Phoenix.

The study was published in Nature today.