A new type of genes related to predisposition to cancer described

More than 100 genes with alterations that cause inherited diseases also increase the risk of cancer. This is the conclusion of a CNIO study, which also shows the relationship of the PAH gene, known for its involvement in a protein assimilation disorder, with lung and liver cancers.

Scientists from the National Cancer Research Center (CNIO), in collaboration with Korean researchers, have proposed a new type of cancer predisposition genes (CPGs). The probability of developing a tumor is greater in those who inherit certain altered variants of one of these genes.

“But those hundred genes only explain 10% of cancer cases. The vast majority of the rest may be related to mutations that we do not know about,” he explains. Solip Park, head of the Computational Genomics Group. Find these other altered variants helps early detection and to develop treatments that counteract its effect.

To discover them, the experts decided to narrow the search to a group with an easily identifiable genetic profile: people who carry genes that, when altered, give rise to a hereditary disease. They are monogenic diseases, that is, they are caused by the alteration of a single gene, such as muscular dystrophy or Gaucher disease.

Park, together with collaborators from several institutions in Seoul, South Korea, has discovered 103 genes in which alterations that cause monogenetic diseases often coexist with other alterations that predispose to cancer.

published in the magazine GenomeMedicine, the study verifies that people with hereditary monogenetic disease mutations in those 103 genes also had a greater number of mutations involved in cancer than the control group (healthy people).

Some of these mutations They are associated with specific types of cancer, such as renal cell carcinoma, B-cell non-Hodgkin lymphoma, breast adenocarcinoma, and medulloblastoma; others, with the propensity for cancer in general. “These 103 genes whose mutations can cause Mendelian diseases can also behave as cancer predisposition genes,” says Park.

Mechanisms against predisposition to cancer

The authors also analyze how defective variants of these genes promote the progression of tumors and cause other diseases, and point to various mechanisms of action, such as distortions of cellular metabolism or the immune response. Some are pathways not considered until now in cancer, which is why they highlight the need to delve deeper into them.

Likewise, they have analyzed in greater detail the PAH gene – known because some of its mutations cause the rare hereditary disease phenylketonuria, which makes the assimilation of proteins and aspartame difficult. Selected because it presented the greatest number of variants likely to give rise to various types of cancer, they have discovered its relationship with squamous cell carcinoma of the lung, tumors of the liver tissue, as well as with other diseases and with a delay in growth.