Forget just watching the sun.
That advice hasn’t changed but everything else might. QIMR Berghofer researchers just pulled together the world’s biggest study of “moliness”—the genetic stuff behind moles—and found more than 250 genes linked to melanoma risk. Published in Nature Communications, it’s a massive leap from what we knew five years ago.
Why Moles Matter
Most people think melanoma comes down to burning in the sun or having fair skin.
Sure. Those are risks. But this study points to something deeper, independent of pigmentation. The new findings highlight biological pathways tied to how the immune system regulates cell growth. Think immune mechanisms failing to hit the brakes on division. Genes linked to unchecked proliferation in breast or prostate cancer are here too.
Understanding how to block these pathways opens the door to drug targets that have nothing to do with sunscreen.
Matthew Law, who leads the Genetics and Skin Cancer lab, isn’t letting up. He notes Australia still has the highest melanoma rate on earth. Roughly 1,400 people die there each year. We’ve got SunSmart guidelines. We have immunotherapies that saved some. Yet half of late-stage patients still don’t respond to those drugs. People still get sick. People still die.
So they looked at moles.
From Benign to Lethal
Both moles and melanoma start in melanocytes—the cells that give skin its color. In a benign mole those cells multiply then stop. Simple. Harmless. In melanoma they don’t stop.
Genetics drives how many moles you get. More moles usually mean higher risk. About one-third of melanomas actually start in a mole you already have.
The team crunched genetic data from over 85,00 Europeans. They found 24 new genetic regions tied to mole count. Five times as many as the previous benchmark from 2018. All but one of those regions also flagged melanoma risk. That leaves us with more than 250 specific genes that need closer looks.
The SIKE1 Connection
One standout is SIKE1.
This gene usually helps manage immune responses to viruses. If it breaks the team thinks the immune system loses its ability to spot and kill rogue melanocytes. They grow unchecked. Cancer grows. SIKE1 could become the next big target for early-stage immunotherapies.
Shanika Jayasinghe, lead author of the paper, sees this as part of a legacy. The institute has tracked twins and genomes for decades. This just adds more detail to why some people are covered in moles and others develop the cancer.
They even built a tool for it: a Polygenic Risk Score.
Screening by the Numbers
This score isn’t just academic.
It identifies people genetically primed for having loads of moles. That means high-risk folks could get flagged earlier. They’d get watched closer. Detection improves before it’s too late.
What’s next?
Larger datasets. More hunting for genetic links. The researchers are also asking a simpler question: do we already have drugs that hit these new pathways? Repurposing old meds is cheaper and faster than inventing new ones from scratch.
Why wait for new chemistry when existing medicine might work if aimed at the right switch?
The credit goes to thousands of participants across thirteen studies, from the QSkin project to the Australian Genetics of Depression Study without their data the genes wouldn’t speak up.
The map is clearer now. We see where the risk hides inside the DNA. But turning a list of genes into a cure that stops the disease in its tracks is still a long way off. For now we have targets. And a reminder that looking at moles isn’t just about aesthetics it’s about survival.
What happens when we actually hit those switches remains to be seen.
