Melanoma genes may indicate broader risk

Monday December 11th, 2017

People who have family members with inherited mutations linked to risk of melanoma also have an increased risk of the disease themselves – even if they do not carry the genetic variants, a new Swedish study has shown.

This phenocopy could result from other shared risk-enhancing genes or environmental factors within the families, say researchers from the Karolinska Institutet, in Stockholm.

Inherited mutations of the tumour suppressor gene CDKN2A are the strongest known risk factors for familial melanoma and mutations in this gene also increase the risk of other cancers.

In this study, which is published in Genetics in Medicine, Swedish and American families with inherited CDKN2A mutations were examined to see if family members who have not inherited the mutation have any higher than normal risk of developing melanoma or other cancers.

They found that only melanoma was more common in the non-carriers in these families compared to the normal population.

Hildur Helgadottir, first author, said: “Phenocopy can be caused by other risk-modifying genes or exposure patterns that increase the probability of the specific phenotype manifesting itself.”

Previous studies have shown that people with the mutation who also have certain pigmentation variants run an even higher risk of melanoma and it has almost exclusively been identified in Caucasians.

“This suggests that dark-skinned people with this mutation probably don’t develop melanoma as often and are therefore not tested for this specific mutation, presumably because they lack the risk-modifying pigmentation variants that increase the risk of melanoma,” said Dr Helgadottir.

The researchers believe that this pigmentation variant also contributes to a higher melanoma risk in the family members who do not carry the mutation.

“Our results suggest that family members that test negatively for their family’s CDKN2A mutation should be informed that they still can have an increased risk of developing melanoma. They should be advised to avoid sunburn, be aware of any change in their moles, and some might even need to be monitored by a dermatologist,” she added.

Helgadottir H, Olsson H, Tucker M et al. Phenocopies in melanoma-prone families with germline CDKN2A mutations. Genetics in Medicine 7 December 2017; doi: 10.1038/GIM.2017.216 [abstract]

Tags: Cancer | Dermatology | Europe | Genetics

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