New Special Interest Group on Genetics - Why?

Genomics and family practice

“The study of genomics ‘addresses all genes and their inter relationships, in order to identify their combined influence on the growth and development of the organism’.”
The World Health Organization definition of genomics

A newly formed WONCA Specialist Interest Group on Genetics has been set up and we hope the topics and themes discussed in this short paper will interest WONCA members (and we look forward to having new members join!).

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Most of us recognise the importance of taking a good and accurate family history which helps us in our decision making – for example, to consider the risk of cancer or heart disease when managing the individual and family in front of us. As we all know, in family practice environmental and behavioral influences are very important, as in the management of obesity and diabetes. One of our tasks in the future is to understand when we should be using genomic information appropriately.

World – wide research and collaboration into genomics is gathering pace, based on sequencing technology which through speed and greater accuracy is leading to the discovery and analysis of potentially causal gene variants in disease. For example, in England there is a large translational research project called the 100,000 Genome Project being led by Genomics England Ltd. Patients with cancer, rare diseases and infectious diseases are having their genome ‘sequenced’. Whole genome sequencing involves coverage of non-coding and coding DNA which goes beyond just focusing on whole exome sequencing i.e the coding section of DNA (or classical genetics study).

Research findings use publically available genomic databases to allow researchers and clinicians to evaluate whether identified new gene variants are pathogenic (i.e. associated with disease). This publically available information has also been used by commercial companies to provide private genomic testing. This use is premature, as there is still much research that is necessary around the clinical utility and validity of using genome tests to inform clinical practice. Also of importance are the ethical and social considerations around the use of genomic data in clinical practice. For example, when is it appropriate to test children?

When should genomic information be shared with relatives? When should individuals carrying high risk genes be offered prophylactic surgery (e.g. BRCA gene in females giving a high risk of breast and ovarian cancer [1] )? What about the use of targeted genomic tests tailored to certain populations (e.g. haemoglobinopathies)? What pre-test counselling should be available, and how should follow up care be financed?

A particular example where all these considerations are needed is the use of circulating fetal DNA in the maternal circulation in testing for Downs’s syndrome. This has been going through rigorous evaluation internationally, and there has been consideration of harms and benefits and limitations of testing. The duty of care provided after testing is crucial, and the key principles around autonomy, beneficence, non-beneficence and justice must apply to the new genomics – otherwise mandatory testing at high costs to those at risk might be a future possibility. For example, in some health systems, female relatives of those with BCRA positive tumours will be offered testing – but then could in future find themselves excluded from some types of life and health insurance, unless a country takes action to agree that test results should not affect insurance [2].

The work around genomics and the need to integrate this into day to day practice will be challenging. As family practitioners we have a wide skill-set including how to manage new information that will need to be applied to patients in their ongoing management of complex conditions. We need to ensure that genomic information is validated for clinical use for the benefit of our patients and their families. There are many examples such as in cancers (e.g. tumour status) and inherited cardiac conditions (e.g. long QT syndromes) where genomic information is powerful and can influence treatment and management. This requires us in family practice medicine to be aware and be ready to apply this new knowledge.

Key points

Family doctors need to know enough about the new genomics to help their patients to make good evidence based choices about tests that could predict their own and their family’s risks.

We need to know what tests are valid and reliable for diagnostics in our own population, and to avoid use of tests which are not yet accurate. If patients present with the results of such tests, we need to help them to understand the implications.

We need to also to advocate for patients who may risk psychological and financial harm if tests are carried out without guarantees of appropriate care if the risk is positive.

Imran Rafi
Convenor WONCA SIG Genetics

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