Surviving melanoma has a new genetic story

The underlying genetic and environmental factors that influence risk and survival of this aggressive skin cancer are fundamental building blocks for melanoma research, diagnosis and treatment, according to Dr Sarah Ward, a leading cancer epidemiologist.

“With a better understanding of the biology and causes of melanoma this knowledge can be built upon and translated into clinical tools that doctors can use to improve patients' lives,” said Dr Ward from the University of Western Australia.

Using an NHMRC Early Career Fellowship, Dr Ward, discovered a particular melanoma risk variant in the IRF4 gene² is strongly associated with melanoma at body sites with a known poor prognosis, tumour thickness and poorer survival rates. Along with her collaborators, they also found a set of variants in the vitamin D-binding protein gene are protective against death in the case of thicker tumours and a variant in the MDM2 gene³ reduced the risk of melanoma death in females. 

To achieve these results, Dr Ward combined data from the WA Melanoma Health Study—a study analysing 1,600 cases, established during her PhD— with international datasets. Through further international collaborations, Dr Ward has also been part of a team identifying 40 new risk variants for getting melanoma.

“This body of research has substantially improved our knowledge of prognostic genetic markers and provides a platform for the development of blood tests to identify genetic markers for survival,” said Dr Ward. 

“Having better prognostic profiles for doctors to use would markedly improve the management of melanoma. I can also see opportunities to identify novel therapeutic targets, which is very exciting,” she said. 

While melanoma genetic screening tools are not yet mainstream, the potential for blood tests and other predictive measures is on the horizon. And this practical application to help patients and families is a key driver behind Dr Ward’s more than 20 years of work in melanoma epidemiology.

“From talking with families as a student and learning more about the disease it became a passion. The more I got involved in the area I’ve wanted to keep going because so many people are affected by melanoma,” said Dr Ward. 

Dr Ward emphasises the importance of working closely with patients and collaborating with researchers to make the most of exciting advancements in genetic technology, particularly as the costs of genetic research have reduced substantially.

“People with melanoma were really enthusiastic about the work and donated their time and came in to do blood tests. Because they embraced the detailed questionnaires and were so forthcoming, we have seen incredible value from this research.

“Working with leading researchers overseas, for example at the Memorial Sloan Kettering Cancer Center in the US, has not only expanded my knowledge but also strengthened international ties in the fight against melanoma.” said Dr Ward.

Next steps

Dr Ward is working towards developing polygenic (multi-gene) risk profiles to determine the combinations of genes that relate to different risks. This kind of profiling would assist doctors to know where on the body a melanoma is more likely to develop, and which melanomas are more likely to metastasise. 

There are some general ‘rules of thumb’—such as patients with thin melanomas (≤1 mm) having excellent prognoses—that warrant closer investigation, according to Dr Ward.

“A small proportion of patients with thin melanoma progress to metastatic disease and present a clinically challenging subset of patients to treat. Being able to identify those patients who are at high genetic risk of fatal thin melanomas means they can be monitored more closely for metastatic disease. The earlier it's diagnosed the less chance that melanoma will metastasise and spread, and that means better survival odds” said Dr Ward.

CIA: Dr Sarah Ward

Institution: University of Western Australia

Grant information: Early Career Fellowship (2017–2021), $419,526.99.