Scientists double understanding of genetic risk of melanoma
28 April 2020
A global collaboration of scientists has more than doubled the known number of regions on the human genome that influence the risk of developing melanoma.
The research, co-led by QIMR Berghofer, the University of Leeds in the UK, and the National Cancer Institute in the US which is part of the National Institutes of Health, has been published today in the prestigious journal Nature Genetics.
Melanoma is a sometimes-deadly skin cancer, with an estimated 350,000 cases worldwide in 2015, resulting in nearly 60,000 deaths.
Joint study leader and QIMR Berghofer statistical geneticist Associate Professor Matthew Law said the researchers identified 33 new regions of the genome and confirmed another 21 previously reported regions that are linked to a person’s risk of developing melanoma of the skin.
“By finding new regions we can now narrow in on the specific underlying genes and better understand the pathways that lead to melanoma,” Associate Professor Law said.
“Two of the new regions we’ve discovered that are linked to melanoma have previously been linked to autoimmune disorders. This provides further evidence that the immune system plays an important role in a person developing melanoma.
“We also found an association between melanoma and common genetic variants in the gene TP53, which is a gene critical in controlling DNA repair when cells divide, and in suppressing cancer.”
Melanoma begins in melanocytes, cells in the skin responsible for making the pigment melanin that gives colour to the skin.
Melanin is able to block some of the harmful effects of UV radiation, which is why people with pale skin are at a higher risk of skin cancer, but the protection is not complete.
Moles also develop from melanocytes, and having a high number of moles is a risk factor for melanoma.
Co-lead author on the study and senior investigator at the National Cancer Institute, Dr Maria Teresa Landi, said the research also uncovered other important clues to the genetic causes of melanoma.
“We used the relationship between moles, pigmentation, and melanoma to identify 31 additional gene regions that potentially influence melanoma risk. For example, one of the regions we identified is involved in melanocyte growth,” Dr Landi said.
“Moreover, we also included people from Mediterranean populations involved in the MelaNostrum Consortium. Most studies of melanoma use people with northern or western European ancestry (e.g. British) and by expanding our analysis to include Mediterranean populations, we will gain a greater understanding of the genetics of melanoma in this highly sun exposed group.
“Larger datasets are needed to find further genes that influence melanoma risk, and in parallel we need functional studies to work out the exact mechanisms that lead to these genes causing melanoma.”
UK based co-lead author, Dr Mark Iles from the University of Leeds’s Institute for Data Analytics, said the researchers examined DNA from 37,000 people who had been diagnosed with melanoma and compared their genetic information to that of nearly 400,000 people with no history of the disease.
“The large population sample made it possible to recognise which regions of the genome were active in people with melanoma,” Dr Iles said.
“The population sample we used is three times larger than any previous genetic study on melanoma risk and gives us strong confidence that the new regions we’ve discovered all play a role in the disease.
“It’s a product of power in numbers. The only way to discover these things is by having such a large study population that spans across the globe, and we’d urge more people to sign up for these large melanoma research projects.”
The researchers said the study reaffirmed the importance of protecting skin from the sun by avoiding UV exposure between the hours of 10 AM and 4 PM, seeking shade, covering up exposed skin, and using sunscreen.
The Nature Genetics study involved the international collaboration of researchers and health professionals from 115 different institutions.
The Australian research and researchers were primarily funded through the National Health and Medical Research Council of Australia and national and state Cancer Councils. Internationally, funding sources included the US National Cancer Institute, and the UK Medical Research Council.
Australians interested in taking part in melanoma research can sign up to QIMR Berghofer’s QSkin Genetics study, which is the largest research study ever conducted on skin cancer and which aims to provide long-term information about the burden of skin cancer in the country.
The Australian Institute of Health and Welfare (AIHW) estimated more than 15,200 new cases of melanoma skin cancer were diagnosed in Australia in 2019, accounting for about 11 per cent of all new cancer cases.
1,725 Australians are estimated to have died as a result of melanoma skin cancer in 2019.