New discoveries about the influence of genes on cancer risk

Most genetic research in cancer focuses on changes that directly affect protein-coding genes. However, it is believed that about 90% of genetic variants associated with cancer are found in non-coding regions, which can regulate and indirectly influence gene activity. They are not well studied because, since they do not encode proteins, it is very difficult to determine how they affect the course of the disease. In this sense, they have remained a mystery to the scientific community.

However, now a team of researchers from SZBL (Shenzhen Bay Laboratory) in China, led by Lei Li, in collaboration with the IDIBELL cell identity gene regulation group led by Dr. Mireya Plass, has gone even further to attempt this. understand the influence of these regions on cancer risk and progression. This collaboration resulted in a publication in the academic journal Nature Communications, the first author of which is Hui Chen, a graduate student, resulting from a joint program between both institutions.

IDIBELL (Institute of Biomedical Research Bellwitge) is located in L’Hospitalet de Llobregat and is one of the institutions CLOSE to the Generalitat of Catalonia.

The study authors analyzed the critical role of variants found in non-coding regions, focusing on those involved in a biochemical process called alternative polyadenylation (APA). In the study, they identified hundreds of these variants involved in tumor growth and cell death, suggesting a critical role in cancer development. Most were associated with breast and prostate cancer, and 62% were not found in previous studies. The fact that such a high percentage corresponds to entirely new discoveries demonstrates the great potential that analysis of these variants has for the discovery of new cancer risk factors, identifying new mechanisms by which genetics may contribute to cancer occurrence and progression.

Two members of the research team. (Photo: IDYBELL)

To focus the study and confirm its utility in a specific case, the team focused on analyzing variants affecting the CRLS1 gene, particularly those associated with breast cancer. As expected, they confirmed that variants that alter the APA process affect the amount of protein made from CRLS1, significantly increasing its amount, which is associated with an increased risk of breast cancer.

The study is titled “A Distinct Class of Cancer Susceptibility Genes Identified by an Alternative Polyadenylation Transcriptome Association Study.” (Source: IDYBELL)