Genetic testing for BRCA1 mutation in the UK

Eccles, Diana M. (2003) Genetic testing for BRCA1 mutation in the UK. The Lancet, 361 (9352), 178-179. (doi:10.1016/S0140-6736(03)12213-1).

Record type: Article

Abstract

Richard Kennedy and colleagues (Sept 28, p 1007)1 provide a comprehensive and helpful review of the clinical and molecular aspects of BRCA1 gene mutation aimed at a general medical audience. However, they make some important inaccuracies that warrant clarification.
They misrepresent the position of the UK Cancer Genetics Group (CGG) of the British Society of Human Genetics. Their panel on “Screening practice for BRCA1 mutations” is based on information from the Cancer Research Campaign (now Cancer Research UK) for use in primary care and endorsed by the CGG. This information from the Cancer Research Campaign gives referral guidelines to help family doctors identify women at increased genetic risk of early-onset breast and ovarian cancer who might warrant further assessment at secondary-care level. However, we wish to make clear that these guidelines are absolutely not intended for selecting women for genetic testing. If the guidelines were to be used for this purpose, they would lead to an intolerable burden on current diagnostic laboratory services with a very low rate of detection for BRCA1 mutations.
We have published other guidelines2 that can be used to select patients at secondary-care level for referral to a specialist cancer genetics service. Such referral would involve a full assessment of pedigree, pathology, and ethnicity to determine the likelihood of a mutation being detected in BRCA1 or BRCA2 and whether molecular genetic testing is appropriate.
Access to diagnostic genetic testing for BRCA1 in the UK is usually only possible through a specialist cancer genetics service, usually sited within the regional genetics service and incorporating a quality assured genetics diagnostic laboratory. Most UK genetic centres will not test individuals for BRCA1 and BRCA2 mutations unless the probability of finding a mutation is above 20%. Although computer models and written guidelines exist for predicting the chance of finding a mutation, it is important to recognise that none of these methods include all the information that an experienced clinician will use to make a judgment about genetic testing.
Use of the term “genetic screening” is confusing. We would prefer to reserve the term screening for population screening programmes. Genetic testing, or perhaps gene mutation analysis, is a more accurate description of the process of searching for a pathogenic mutation in a DNA sample from a carefully preselected patient.
Interpretation of the result of the genetic testing will require much more information about the individual and their family history than is provided by the test sample alone. Although the outcome of looking for pathogenic mutations in an individual may be falsely negative, once the specific pathogenic mutation in the family has been identified, the result of predictive testing for an unaffected relative is highly accurate. It is important to clarify this commonly misunderstood distinction.

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