Immune system plays a role in mole formation and melanoma risk

Investigating the genetics of moles was one of the foundational aims of the Brisbane Longitudinal Twins Study. After leading the discovery of some of the first known genes for both mole count and melanoma, Professors Martin and Duffy published the world’s largest genetic study of nevus count in 2018.

In 2025, PhD Student Shanika Jayasinghe and Associate Professor Matthew Law have built on this work, leading an even larger study of nevus count, including 85,967 individuals of European ancestry.

While previous studies identified five genomic regions linked to mole count, these regions were mostly associated with pigmentation pathways, meaning the genes influenced skin colour and how the body responds to UV exposure.

The latest study, uncovered 24 new genomic regions, associated with mole count, in addition to the five previously known. One notable gene is SIKE1 which plays a role in immune response, not pigmentation.

Mole count is a strong predictor of melanoma risk, but these findings show that the risk is not only about skin colour or UV sensitivity. The discovery of genes like SIKE1 suggests that immune system pathways also play a role in mole formation and melanoma risk. This broadens our understanding of melanoma biology and could lead to new prevention strategies and treatments that go beyond sun protection.

This work is currently under review at Nature Communications.