MedicalResearch.com Interview with:
Dr Ranjit Manchanda
Consultant Gynaecological Oncologist, St Bartholomew’s Hospital, London, UK
Honorary Sr Lecturer, Women’s Cancer, EGA Institute for Women’s Health, University College London, UK and
Professor Ian Jacobs
Vice President, The University of Manchester
Dean & Head School of Medicine
Faculty of Medical & Human Sciences, Director
MAHSC (Manchester Academic Health Science Centre)
Medical Research: What is the background for this study? What are the main findings?
Dr. Jacobs: Background- Women carrying a BRCA1/2 gene alteration have a very high risk of developing breast and ovarian cancer and men carrying this alteration have an increased risk of prostate and breast cancer. Approximately 45-65% women who have this inherited genetic change will develop breast cancer and 15-35% ovarian cancer. They also have a 50% chance of passing these genes on to their children. At risk individuals can access available options of screening and prevention through the National Health Service (NHS). Some population groups across the world are known to have a higher frequency of BRCA 1/2 gene alterations than others. One example is Ashkenazi Jews who have a 1 in 40 likelihood of having a BRCA1/2 gene alteration. This is 10-20 times higher than in the general non-Jewish population.
At present in the UK, genetic testing is available within the NHS to individuals who have a strong family history of cancer. However, many people are not aware of their family history or its significance and do not seek advice. Many other individuals with BRCA1/2 gene alterations do not have a family history at all. The current approach misses a large number of people at risk who could benefit from knowing about their BRCA 1/2 mutation status and the ability to access opportunities for prevention or screening. In order to address this the GCaPPS study has investigated the best method of screening for risk of inherited (familial) cancer by exploring the alternative approach of offering the genetic test to all men and women >18 years in the Ashkenazi Jewish population. It does so by comparing the benefits and disadvantages of: (i) The current system of testing only those with a family history and (ii) The new option of testing everyone in the population.
Main Findings: Over half of the BRCA1/BRCA2 carriers detected did not give a strong family history of cancer and would not have been identified by current family history based testing criteria used in the NHS (National Health Service) in the UK and most health systems internationally. Reassuringly population-based genetic testing in Ashkenazi Jews did not adversely affect short term psychological health or quality-of-life. A health economic analysis indicated that population-based screening for BRCA-mutations in Ashkenazi Jewish women ≥30years would be highly cost-effective compared to the traditional family history based approach. Such an approach if implemented could reduce the incidence of and deaths from breast and ovarian cancer as well as reducing cost and save the NHS funds.
Medical Research: What should clinicians and patients take away from your report?
Dr. Jacobs: The current family history based criteria used for identifying people at risk of carrying BRCA 1 and BRCA2 mutations miss >50% of the people at risk.
Offering testing to the whole Ashkenazi Jewish population of can detect >50% more people carrying BRCA mutations, compared to the existing family history based testing (even if all people with a family history seek advice). A population based approach to genetic testing in Ashkenazi Jews did not adversely affect short term psychological health or quality-of-life.
A health economic decision analytical model demonstrated that offering screening to all Ashkenazi Jewish women aged ≥30 years for BRCA mutations is highly cost effective and would be likely to save health services money, as well as and reducing the incidence of and deaths from breast and ovarian cancer.
Such an approach in Ashkenazi Jewish women ≥30years is highly cost-effective compared to the traditional family history based approach.
Our findings have potentially important policy implications for BRCA testing in the Jewish population, which can save lives in the community and money for the NHS. This will require a change in the current paradigm of a family history based approach to genetic testing in the Jewish population. Any change in practice in the UK would depend on decision making bodies like NICE, commissioners of NHS care, Regional genetics services, etc. They will need to take cognizance of these results and other emerging data in the literature.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Jacobs: Our data are of immediate relevance and benefit to the Ashkenazi Jewish population but cannot be directly extrapolated to the rest of the general population. As the cost of testing falls and the acceptance and understanding of this type of health intervention evolves in our societies, it is likely to become an increasingly important area for research and evaluation. Future research studies are needed to explore the impact of genetic testing and risk stratification in the general (non Jewish) population.
Citation: Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial
Ranjit Manchanda, Kelly Loggenberg, Saskia Sanderson, Matthew Burnell, Jane Wardle, Sue Gessler, Lucy Side, Nyala Balogun, Rakshit Desai, Ajith Kumar, Huw Dorkins, Yvonne Wallis, Cyril Chapman, Rohan Taylor, Chris Jacobs, Ian Tomlinson, Alistair McGuire, Uziel Beller, Usha Menon, and Ian Jacobs
JNCI J Natl Cancer Inst (2015) 107 (1): dju379 doi:10.1093/jnci/dju379