New study identifies hundreds of genes related to mole prevalence

https://youtu.be/wEF0HsABDrQ

The world’s largest genetics study of ‘moliness’ has uncovered hundreds of genes that play a role in the growth of both moles and melanoma, a discovery that could lead to new ways to prevent and treat the deadliest form of skin cancer.

These findings, published in Nature Communications, come from research by a team at QIMR Berghofer Medical Research Institute in Herston, Australia.

The team found risk genes linked to biological pathways that could lead to the development of a mole or melanoma. These include an immune response pathway that may be failing to control cell growth, and genes implicated in harmful cell proliferation in other types of cancer, such as breast cancer, prostate, and brain cancers.

Working out how to stop these risk pathways could lead to new melanoma drug targets and prevention strategies that go beyond sun protection, the researchers say.

In a press release, Associate Professor Matthew Law, PhD, Team Head of QIMR Berghofer’s Genetics and Skin Cancer Lab, said that research has made significant inroads. However, Australia still has the world’s highest incidence of melanoma. Around 1,400 Australians die from the complex disease each year.

“We know how to reduce sun exposure and risk through SunSmart behaviours, and new immunotherapies have greatly improved survival rates. But people still get melanoma, and people still die from melanoma,” Dr. Law said.

“Existing immunotherapies fail to work for half of all patients with late-stage melanoma, so we need to find other ways to target the disease. By studying moles, we’re learning more about the biology of melanoma so we can find new ways of controlling it.”

The QIMR Berghofer research analyzed data from more than 85,000 participants of European ancestry, identifying 24 new genetic regions that determine the number of moles a person has. This is a five-fold increase over the five areas identified in an earlier 2018 study, also led by QIMR Berghofer researchers.

All but one of the genetic regions for mole count also play a role in melanoma. The team pinpointed more than 250 key genes in these regions to prioritize for further research.

One of the new genes, SIKE1, regulates immune responses to viral infections. The researchers think it could enable the development of melanomas by malfunctioning and affecting the immune system’s ability to detect and destroy melanocytes that are multiplying abnormally. This could be a promising target for an immunotherapy that could prevent early-stage melanoma growth.

The researchers used the study insights to create a Polygenic Risk Score (PRS) for moliness to predict those who are genetically more likely to have a large number of moles. This PRS could be integrated into melanoma screening tools in the future to improve their accuracy in identifying those at high risk, enabling them to receive additional monitoring.

The next step is to analyze even larger datasets to identify additional genetic regions involved in melanoma. The researchers are also searching for existing medications that could potentially target the newly identified biological pathways.