2024-01-27 05:15:16
The results of a recent study reveal a type of cancer predisposition genes and suggest more mechanisms of action for those already known.
About a hundred so-called cancer predisposition genes (CPGs) are known. The probability of developing cancer 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 other cases may be related to mutations that we do not know about,” explains Solip Park, head of the Computational Cancer Genomics Group at the National Cancer Research Center (CNIO) in Spain. Finding these other altered variants helps with early detection and developing treatments that counteract their effect.
To discover them, Park, Seulki Song of the CNIO and their colleagues narrowed 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 (they are caused by the alteration of a single gene), such as muscular dystrophy or Gaucher disease – in which fat accumulates in various cells.
Park, Song and their collaborators at several institutions in Seoul, South Korea, have discovered 103 genes in which alterations that cause monogenetic diseases often coexist with other alterations that predispose to cancer.
The study found 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 (the group of healthy people). 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 the propensity for cancer in general.
Thus, the authors of the study have come to the conclusion that these 103 genes whose mutations can cause Mendelian diseases can also behave as cancer predisposition genes, in the words of Park.
Solip Park. (Photo: Laura M. Lombardía. CNIO)
In their research, the study authors have also analyzed how defective variants of these genes promote the progression of tumors and cause other diseases. Judging by the evidence collected, various mechanisms of action are involved, such as distortions of cellular metabolism or the immune response. Some are mechanisms not considered until now in cancer, which is why the authors of the study highlight the need to delve deeper into them.
They have analyzed in greater detail the PAH gene (known because some of its mutations cause the rare hereditary disease phenylketonuria, which makes it difficult to assimilate proteins and aspartame). They selected it because it had the greatest number of variants likely to give rise to various types of cancer and 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.
“Our study shows for the first time how genes associated with a series of inherited monogenic diseases can increase the risk of cancer. Likewise, it reveals mechanisms of tumor generation triggered by new and previously unknown cancer predisposition genes,” says Solip Park.
The authors of the study point out the need to continue investigating the role played in cancer by these 103 genes, whose clinical relevance was until now limited to other hereditary diseases. In particular, the relationship of each variant with the different types of cancer will still have to be specified.
However, based on the results, it would be advisable for people carrying the alterations that cause the monogenic diseases studied to participate in already established cancer prevention programs.
The study is titled “Systematic analysis of Mendelian disease-associated gene variants reveals new classes of cancer-predisposing genes.” And it has been published in the academic journal Genome Medicine. (Source: CNIO)
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