New Genetic Regions Linked to Risk of Melanoma

Skin cancer is the most common type of cancer. There are several types of skin cancer, but melanoma causes most skin cancer deaths. Melanomas are tumors that arise from melanocytes, the cells that produce your skin’s natural color (pigment).

Melanoma is caused by a combination of environmental and genetic factors. The biggest environmental risk factor for developing melanoma is exposure to ultraviolet (UV) radiation from the sun. UV radiation damages DNA. However, other factors are also linked to increased risk for melanoma, including family history, a light skin complexion, and having a lot of freckles and moles.

Most cases of melanoma are sporadic, meaning that the genetic changes that led to the cancer were not inherited. Rather, the pigment cells accumulated these changes over a lifetime. But there are also inherited genetic changes that can increase your risk for skin cancer. Previous genome-wide association studies in people of European descent identified 21 genetic loci (regions of the genome) linked to melanoma risk, and other approaches identified another 12.

To evaluate genetic risk of melanoma more broadly for people across the globe, an international team of researchers led by Drs. Maria Teresa Landi at NIH’s National Cancer Institute (NCI), Matthew Law at QIMR Berghofer, and Mark Iles at the University of Leeds compared DNA from nearly 37,000 people with melanoma to 375,000 healthy people. Study participants were from the United States, United Kingdom, Australia, northern and western Europe, and the Mediterranean. Results were published in Nature Genetics.

The team identified 54 loci that were associated with melanoma, half of which were previously linked to a person’s risk for melanoma.

By combining their meta-analysis with genetic data linked with known risk factors, they identified another 31 loci that influence melanoma risk. These included eight linked to melanoma and mole count, 17 to melanoma and light hair color, and four to melanoma with both mole count and light hair color.

They found no major differences in the results between people living in different geographic regions.

“We used the relationship between moles, pigmentation, and melanoma to identify 31 additional gene regions that potentially influence melanoma risk,” says Landi.

“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,” Iles says.

“By finding new regions we can now narrow in on the specific underlying genes and better understand the pathways that lead to melanoma,” Law explains.

More studies will be needed to learn how these genes are functionally involved in the development of melanoma.

Reference

Landi et al. (2020). Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility. Nature Genetics. DOI: https://doi.org/10.1038/s41588-020-0611-8

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