Women who are BRCA1 and BRCA2 negative but have a family history of ovarian, breast and other cancers should be tested for mutations in two other genes, British researchers say.
A new study has found that testing for homologous recombination (HR) and mismatch repair (MMR) genes is highly effective.
Scientists from The University of Manchester, who conducted what is the largest study of cancer causing genetic mutations in ovarian cancer to date, say this would save lives.
The research team tested 277 women with ovarian cancer whose close relatives had been diagnosed with the disease over their lifetime.
They found that of those who tested negative for BRCA1 and 2 gene mutations, 22% were positive for HR and MMR, which is twice as high as the equivalent detection rate in breast cancer.
While there are routine tests for cancer causing BRCA1 and BRCA2 genes, which are associated with a lifetime risk of 20% to 60% and 10% to 25% respectively, there are no routine tests for the other genes.
Writing in *Genetics in Medicine*, the authors say HR genes work with BRCA genes and MMR genes are associated with Lynch syndrome, which increases the risk of different cancers.
BRIP1, one of the HR genes, was the single gene responsible for most cancers after BRCA1 and BRCA2.
They say identifying the mutations in people with advanced cancer could allow doctors to prescribe them personalised gene therapies that specifically target the tumour.
Identifying the defective genes in close relatives, such as daughters, nieces, aunts or cousins, could give them the choice of mitigating risk with preventative surgery.
Lead author Dr Nicola Flaum 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."�
Flaum N, Crosbie EJ, Edmondson R et al. High detection rate from genetic testing in BRCA-negative women with familial epithelial ovarian cancer. *Genetics in Medicine* 28 September 2022
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