Current detection strategies are found to have identified only 2.6% of the BRCA gene mutation carriers in the Greater London population, according to a recent study published in the Journal of Medical genetics. The findings of the study, performed by researchers from the BCI’s Centre for Experimental Cancer Medicine, led by Dr Ranjit Manchanda, suggest that enhanced and new approaches are required to maximise the opportunity for breast and ovarian cancer prevention.

BRCA1 and BRCA2 mutations are associated with an increased risk of breast and ovarian cancer. A recent study has shown that about 72 and 69% of women who inherit a harmful mutation in the BRCA1 and BRCA2 genes, respectively, develop breast cancer by 80 years of age. Additionally, 44 and 17% of women who inherit a harmful mutation in the BRCA1 and BRCA2 genes, respectively, develop ovarian cancer by 80 years of age. Identifying mutation carriers is therefore critical to reduce the number of BRCA-associated cancers.

BRCA1 and BRCA2 are genes that code for proteins that suppress cancer development, known as ‘tumour suppressor’ proteins. BRCA1 and BRCA2 usually repair damage to DNA; however, mutations in these genes can result in proteins that do not function properly, which may result in the accumulation of more DNA damage and cancer development.

Identifying the number of BRCA mutation carriers

In order to evaluate the number of mutation carriers who have been identified by the NHS, the researchers- including those from Guys Hospital, St George’s Hospital, the Wolfson Institute of Preventive Medicine, QMUL, University College London, University of Cambridge, London School of Hygiene & Tropical Medicine and University of New South Wales, Australia- collected data on BRCA mutation carriers from NHS laboratories that had been obtained between 1994 and 2014.

Previous research has enabled the estimation of the number of BRCA mutation carriers in the population. Using specialised software, the researchers were able to use this estimation to determine the number of carriers in different postcode sectors in the Greater London population (~16 million). By combining this information with the number BRCA carriers identified by the NHS, the researchers found that only 2.6% of carriers in the general population and 10.9% of carriers in the Ashkenazi Jewish population across Greater London were identified between 1994 and 2014.

Researchers developed forecasting models to predict time to identification of the residual pool of BRCA carriers. They found that carriers in the population may never be identified by continuing at the current rates of detection. Even doubling current detection rates would only identify all ‘detectable’ BRCA-carriers in the general population by year 2181.

Enhanced approaches are required

The findings of the study, supported by the Eve Appeal, suggest that the current rates of detection are inadequate to maximise the opportunity offered by technology for cancer prevention.

Dr Manchanda said:

Effective options for preventing cancers exist for women at high risk. The current system is not working well enough to maximise the opportunity offered by technology and modern medicine for cancer prevention in high risk women. We need to explore new strategies like population testing as well as enhance awareness and implementation of ongoing strategies of testing at cancer diagnosis.

The burden of disease is increasing, with the number of breast and ovarian cancer cases in the UK expected to rise by 24 and 27%, respectively, in the next 20 years. The findings of the present study support previous work and ongoing research, which suggest that whole-population testing may be a feasible and cost-effective approach to identify mutation carriers.

The identification of carriers provides opportunity for early diagnoses, more effective treatment and cancer prevention. It is essential to enhance current detection strategies by improving implementation and increasing awareness in the population, and to explore novel methods of detection. The team believe that more research is required to evaluate barriers and attitudes to gene testing in a bid to increase the rates of early detection and breast and ovarian cancer prevention.