A faulty copy of a DNA repair gene called RAD51D increases a woman’s risk of developing ovarian cancer to 1 in 11 compared to 1 in 70 in the general population, according to a study led by Professor Nazneen Rahman at The Institute of Cancer Research. Furthermore, because a class of drugs already exists that shows potential in targeting affected cells, there is hope that personalized treatment will be available soon.
RAD51D repairs damaged DNA. When the gene is defective, a critical repair pathway is lost. This allows damaged DNA to collect in cells, which then increases the cancer risk.
For the study, an examination of DNA from women in 911 families with ovarian and breast cancer was performed by Rahman and colleagues. These data were compared with the DNA from a control group of 1060 people from the general population.
Eight inactivating RAD51D mutations were found in unrelated women with cancer, compared with only 1 mutation in the control group.
The association between mutation and cancer was principally specific to ovarian cancer, with 3 mutations discovered in 59 of the families with 3 or more individuals with ovarian cancer.
It was also observed that cells lacking the RAD51D gene were responsive to treatment with a new class of cancer drugs, the PARP inhibitors.
PARP inhibitors reduce the actions of the enzyme Poly ADP ribose polymerase (PARP), a protein that affects many cell processes related to DNA repair and programmed cell death.
Clinical trials with PARP inhibitors are already presenting promising results in the treatment of breast and ovarian cancers involving altered BRCA1 and BRCA2 genes, which also is related to repairing damaged DNA.