CNIO researchers discover hundreds of genes that predispose to cancer

Study National Cancer Research Center (CNIO), in collaboration with Korean researchers, proposes a new type of cancer susceptibility genes and proposes additional mechanisms of action to those already known.

About a hundred so-called cancer susceptibility genes (CPGs) are known. Those who have inherited certain altered variants of one of these genes are more likely to develop cancer.

“But These hundred genes explain only 10 percent of cancers.. The vast majority of other cases may be due to mutations that we do not know about,” explained Solip Park, head of the computational cancer genomics group at the National Center for Cancer Research (CNIO). Detection of these other altered variants helps in early detection. and develop treatments that counteract its effect.

To discover them, Park decided to narrow his search to a group with an easily identifiable genetic profile: people who carry genes whose changes lead to a hereditary disease. These are monogenic diseases caused by changes in a single gene, such as muscular dystrophy or Gaucher disease, in which fat accumulates in different cells.

Therefore, Park, together with employees from several institutions in Seoul (South Korea) discovered 103 genes, changes in which cause monogenetic diseases. They often coexist with other changes that predispose to cancer.

The study found that people with inherited monogenetic mutations in these 103 genes also have more cancer-linked mutations than healthy controls.

Some of these mutations are associated with specific 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.

Thus, the authors in their study, published in the journal Genomic Medicine, suggest that “these 103 genes whose mutations can cause disease Mendelian genes can also behave as cancer susceptibility genes.

In their research, they also analyze how defective variants of these genes contribute to the progression of tumors and cause other diseases, and point to different mechanisms of action, such as distortions in cellular metabolism or the immune response. Some mechanisms have not yet been addressed in cancer. Therefore, the authors emphasize the need for a more in-depth study of them.

They took a closer look at the PAH gene, known for its mutations causing the rare inherited disease phenylketonuria, which makes it difficult to digest proteins and aspartame.

They chose it because it had the largest number of variants that can cause various types of cancer and found its association with squamous cell lung cancer.tumors of the liver tissue, as well as other diseases and growth retardation.