Are You at Risk? New Study Reveals Hidden Cancer Dangers in Your Genes - Video

With a focus on the "cancer protection" gene RAD51C, researchers from the Wellcome Sanger Institute and their partners discovered over 3,000 deleterious genetic alterations that may interfere with its function and raise the risk of aggressive subtypes of breast cancer four times as well as ovarian cancer six times. Data analysis from extensive health databases validated these conclusions.

The results, can be utilized right away to assist medical professionals and diagnostic laboratory scientists in more accurately estimating the risk of cancer, particularly in those with a family history of malignancies.

The study also identified regions of the protein essential for its function, pointing to new roles in cancer development and potential therapeutic targets.

The RAD51C gene encodes a protein crucial for DNA repair. Variants in this gene that stop the protein from working are known to increase the risk of breast and ovarian cancers and rarely, if there are two harmful gene changes are present, may result in Fanconi Anaemia, a severe genetic disorder. Women with a faulty RAD51C gene face a 15 to 30 per cent lifetime risk of developing breast cancer and a 10 to 15 per cent risk of developing ovarian cancer.

In this new study, researchers from the Wellcome Sanger Institute and their collaborators set out to understand the effect of 9,188 unique changes in the RAD51C gene by artificially altering the genetic code of human cells grown in a dish, in a process known as 'saturation genome editing'. They identified 3,094 of these variants that may disrupt the gene's function and increase cancer risk, with an accuracy above 99.9 per cent when compared to clinical data.

By mapping the protein structure, the team also identified crucial surface areas of RAD51C essential for its DNA repair function. These regions may interact with other, yet-to-be-identified proteins or play a role in processes such as phosphorylation, offering valuable insights for drug development and potential new treatment targets.

The study also revealed the existence of 'hypomorphic alleles' - a type of variant that reduces the RAD51C gene's function without completely disabling it. These appear to be more common than previously thought and may significantly contribute to breast and ovarian cancer risk.

Rebeca Olvera-Leon, first author of the study at the Wellcome Sanger Institute, said: "This research demonstrates that genetic risk for breast and ovarian cancer isn't a simple yes-or-no scenario, but exists on a spectrum based on how genetic changes affect protein function. With a more comprehensive understanding of how RAD51C genetic variants contribute to cancer risk, this opens up new possibilities for more accurate risk prediction, prevention strategies, and potentially targeted therapies."

Dr Andrew Waters, co-senior author of the study at the Wellcome Sanger Institute, said: "This work demonstrates the power of analysing genetic variants on a large scale within their genomic context. Not only can we understand how cancer-related DNA changes affect patients, helping with clinical decisions, but we can also explore how these variants impact the gene's function at a detailed molecular level. This provides important insights into how proteins work and how genes evolve over time."

Reference: Olvera-León, R., Zhang, F., Offord, V., Zhao, Y., Tan, H. K., Gupta, P., ... & Adams, D. J. (2024). High-resolution functional mapping of RAD51C by saturation genome editing. Cell.