Genome Editing and Hereditary Cancer Research

The International Agency for Research on Cancer’s Cancer Statistics
• Estimates suggest one in five individuals has a lifetime risk of developing cancer.
• The agency estimates that one in nine males and one in 12 females will die of cancer.
• In 2022, the agency counted 20 million new cancer cases and 9.74 million cancer-related deaths.
• By 2045, the agency predicts a rise to 32 million new cases and 16 million deaths, with Asia accounting for almost half of all cases worldwide.
Hereditary Cancers and Genetic Mutations
• All cancers occur due to genetic mutations in the body’s genome.
• Around 10% of all individuals with any cancer could have inherited a genetic mutation.
• The prevalence of inherited mutations is higher among individuals with ovarian cancer (20%), 10% among those with breast, colorectal, lung, or prostate cancers, and a lower 6% among those with cervical cancer.
The BRCA Genes
• Scientists have extensively documented hereditary cancers, with over 50 genetic syndromes predisposing individuals to cancer.
• The discovery of the BRCA1 and BRCA2 DNA-repair genes in 1994 and 1995 bolstered our understanding of hereditary cancer syndromes.
• Hereditary breast-ovarian cancer syndrome is a relatively common cancer predisposition syndrome caused by mutations in the BRCA1 and BRCA2 genes.
• BRCA1 and BRCA2 mutations are present in around one in every 400 individuals, increasing the risk of developing cancer.
Target Therapies for Cancers
• Targeted therapies available today for individuals who develop cancers due to mutations in the BRCA genes or in genes implicated in other DNA-repair pathways.
• Poly (ADP-ribose) polymerase (PARP) inhibitors, a new class of chemotherapy drugs, have shown promising results from recent clinical trials.
Risk is a Spectrum
• Researchers at the Wellcome Sanger Institute in the UK identified more than 3,000 genetic changes in the RAD51C gene that may significantly increase the risk of breast and ovarian cancer.
• The researchers used a technique called saturation genome editing to examine 9,188 variants, revealing that 3,094 could disrupt the gene’s function and increase ovarian cancer risk six-fold and aggressive breast cancer risk four-fold.
• The study confirmed genetic risk lies on a spectrum influenced by the extent to which genetic changes affect protein function.