Spanish scientists have discovered a new type of cancer-predisposing genes

Scientists at the National Cancer Research Center (CNIO), in collaboration with Korean researchers, have proposed a new type cancer susceptibility genes (CPG). Those who have inherited certain altered variants of one of these genes are more likely to develop a tumor.

“But these hundreds of genes explain only 10% of cancers. The vast majority of the rest may be due to mutations that we don’t know about,” he explains. Solip Park, head of the computational genomics group. Find these other modified options helps early detection and develop treatments that counteract its effect.

To find them, experts decided to narrow the search to a group with an easily identifiable genetic profile: people who carry genes that, when changed, lead to an inherited disease. These are monogenic diseases, that is, caused by changes in one gene, such as muscular dystrophy or Gaucher disease.

Park, along with collaborators from several institutes in Seoul, South Korea, discovered 103 genes in which changes that cause monogenetic diseases often coexist with other changes that predispose to cancer.

Those who have inherited certain altered variants of any of these genes are more likely to develop the tumor.

Published in the magazine Genomic medicineThe study confirms that people with inherited monogenetic disease mutations in these 103 genes also had more cancer-related mutations than controls (healthy people).

Something from this mutations They are associated with certain types of cancer, such as renal cell carcinoma, B-cell non-Hodgkin lymphoma, breast adenocarcinoma, and medulloblastoma; others, with a tendency to cancer in general. “These 103 genes whose mutations can cause Mendelian diseases may also behave as cancer susceptibility genes,” Park says.

Mechanisms against cancer susceptibility

The authors also analyze how defective variants of these genes promote tumor progression and cause other diseases, and point to different mechanisms of action, such as disturbances in cellular metabolism or the immune response. Some pathways have not been addressed in cancer so far, highlighting the need to study them in more depth.

They also took a closer look at the PAH gene, known because some of its mutations cause the rare inherited disease phenylketonuria, which makes it difficult to digest proteins and aspartame. Selected because it represented the largest number of variants that can cause different types of cancer, they found an association with squamous cell lung cancer, liver tumors, as well as other diseases and growth retardation. .

Link: Song, S., Koh, Y., Kim, S. and others – “Systematic analysis of gene variants associated with Mendelian diseases identifies new classes of cancer susceptibility genes.” Magazine Genomic medicine, 2023 | DOI: 10.1186/s13073-023-01252-w.