Scientists from the University of Manchester have discovered that two gene families are linked to epithelial ovarian cancer risk.
Epithelial ovarian cancer is the most common type of ovarian cancer. Statistics show that around 90 out of 100 tumours of the ovary are epithelial. There are different types of epithelial ovarian cancers, including serous, which is the most common; endometrioid, which can be linked to endometriosis; clear cell, which is rare but also potentially linked to endometriosis; mucinous is rare and difficult to diagnose, and there are also unclassified cases.
The study funded by Cancer Research UK and published in the journal Genetics in Medicine is the largest study of ovarian cancer-causing genetic mutations to date. It showed that testing the two gene families linked to a lifetime epithelial ovarian cancer risk of 5-20% has a much higher detection rate.
Testing for gene mutations
Routine testing for mutations in homologous recombination (HR) and mismatch repair (MMR) genes in women with family members with breast and epithelial ovarian cancer could save lives.
The researchers tested 277 women with epithelial ovarian cancer whose close relatives already had a diagnosis in their lifetime. Of those who tested negative for BRCA1 and 2 gene mutations, 22% were positive for HR and MMR, twice as high as the equivalent detection rate in breast cancer cases.
“This project is the most detailed genetic study of familial ovarian cancer to date. And we show that two gene families with a lifetime epithelial ovarian cancer risk of between 5% and 20% are even more present in these families than we thought,” commented Dr Nicola Flaum.
Presently, doctors will routinely test for cancer-causing BRCA1 and BRCA2 genes, which are associated with a lifetime risk of 20-60% and 10-25% respectively. They do test for other genes, but this is not routine.
HR genes work with the BRCA and MMR genes, which are associated with Lynch syndrome, a condition passed from parents to children that consequently increases the risk of different cancers.
Furthermore, one of the HR genes called BRIP1 was the singular gene responsible for causing the most cancers after BRCA1 and BRCA2.
Personalised gene therapies for epithelial ovarian cancer
Identifying these mutations in people with advanced epithelial ovarian cancer could mean doctors could prescribe personalised gene therapies to target the tumour. Additionally, spotting the defective genes in close relatives at an earlier state could give the patient more time to have preventative surgery.
Dr Nicola Flaum, the lead author of the study from The University of Manchester, said: “This project is the most detailed genetic study of familial ovarian cancer to date. And we show that two gene families with a lifetime epithelial ovarian cancer risk of between 5% and 20% are even more present in these families than we thought. That is why we think as a matter of routine, women who are BRCA1 and BRCA2 negative with a family history of ovarian, breast and other cancers should be tested for these other gene mutations. Wider genetic testing of women with familial ovarian cancer is essential to both optimise their treatment and enable prevention of disease in family members.”
She added: “Ovarian cancer has a poor survival rate as it is usually diagnosed late. That is why it is important to test asymptomatic family members as well so they can be offered risk management strategies. We urge patients to tell the doctors about their familial history so they and their relatives can be tested.”