UK-first study to assess role of whole-genome
screening in primary care

People in the UK will for the first time have their entire genetic code read from samples taken at a GP practice as part of a pioneering study to assess the potential benefits of screening for gene faults that increase the risk of disease.

Researchers aim to screen the genomes of around a thousand GP patients in London to assess the feasibility of testing for faulty genes that increase the risk of cancer and heart disease, and how acceptable screening is to patients.

The initiative, launched today (Friday), will aim to establish whether whole-genome sequencing in a healthy population can have a significant impact on people’s health by helping diagnose cancer, heart disease and other illnesses much earlier.

The new study is the first in the UK to assess whether whole-genome sequencing can be used to screen for a range of genes linked to disease or response to medicines, and what effect this has on patients’ healthcare. If successful, it could be a key step towards much more routine use of genetic testing to predict and manage patients’ future health in the NHS.

The 90S Study

The research, called the 90S Study, is led by Professor Ros Eeles, a world-leading expert in cancer genetics at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and Dr Michael Sandberg, a GP at 90 Sloane Street – a private GP practice from which patient volunteers will be recruited.

The study involves further experts from The Institute of Cancer Research (ICR) and The Royal Marsden plus expert cardiologists at Royal Brompton Hospital and is under the auspices of the 90 Sloane Street Genetic centre, a collaborative team of five consultant geneticists.

The first 20 patients will be evaluated for the psychological effects of genetic screening as part of a study funded by donations to The Institute of Cancer Research (ICR) and through support from the NIHR Biomedical Research Centre at The Royal Marsden and the ICR, and 90 Sloane St.

The study will then be expanded to around a thousand patients initially recruited at 90 Sloane St, with NHS GP practices lined up to join the pilot in a subsequent stage. Integrating genomic medicine into primary care There has been huge progress over the last 25 years in identifying inherited causes of disease, such as BRCA gene faults predisposing to breast and ovarian cancer, and Lynch syndrome gene alterations which increase the risk of bowel and uterine cancer.

In cardiovascular disease, familial hypercholesterolaemia causes inherited high cholesterol, variants in the long QT genes can cause dangerous heart rhythm disturbances and other gene faults can cause heart muscle disorders. Advances in the technology to read people’s DNA have made it so much faster and cheaper that it is now practical to screen patients by sequencing their whole genome.

There is considerable public interest in genetics, as shown by the growing popularity of unreliable and simplistic direct-to-consumer tests. But until now, there has been no thorough investigation of how properly controlled and validated genomic medicine could be integrated into primary care in the UK.

In the new initiative, researchers will analyse the entire genetic code of people attending a GP surgery and report on around 600 separate genetic changes known to be associated with disease, or in some cases affect how patients respond to or metabolise certain medicines.

The study is looking only for ‘actionable gene alterations’ which if detected would alter choices for an individual such as lifestyle improvements, specific screening and sometimes targeted treatments. It will not report on risk of diseases for which there are no current actions that can be taken.

Different to direct-to-consumer testing

The study will assess how frequently genetic alterations are picked up by whole-genome sequencing in people with a family history of cancer or heart disease compared with people who do not – half of the volunteers will be from each group.

The researchers aim to expand the study to incorporate other partner GP practices and widen the possibility for people to take part. Evidence gathered will inform decision making around the use of whole-genome sequencing in a primary care setting – in both the NHS and private practice.

The initiative differs fundamentally from direct-to-consumer testing in that patients will receive genetic screening as part of a detailed medical review. All patients will also have an on-site echocardiogram – a heart ultrasound – to provide crucial extra information and to reassure those with some genetic risk of heart disease but no signs that this is actually affecting their health.

The project leaders are not suggesting that future population genetic screening would necessarily need to be done with this level of resources – and they will be looking for ways of simplifying and improving processes to be suitable for large-volume NHS screening.

‘Intervene early to improve patients’ health’ Study leader Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, and Consultant in Clinical Oncology and Oncogenetics at The Royal Marsden NHS Foundation Trust, said: “We’ve seen incredible progress over the last quarter of a century in identifying genetic alterations that are linked to the risk of disease, opening up the possibility to intervene early to improve patients’ health.

“Our new initiative takes cutting-edge science on the genetics of disease into a primary care setting, by sequencing patients’ entire genomes from samples taken at a GP surgery and testing for the presence of 600 key genetic alterations.

What we hope is that genetic screening is practical as a way of picking up genes associated with cancer and heart disease, is psychologically acceptable to patients, and can alter the way they are managed by their GP.

“The project will give us crucial information about whether genetic screening in primary care could be feasible, and how we should go about seeking to implement it within the NHS.”

‘Target and identify high-risk patients’ Dr Michael Sandberg, General Practitioner at 90 Sloane Street and Co- Principal Investigator for the 90S Study, said: “Genetic information will help us to target and identify high-risk patients, so as to find diseases at an earlier stage and give greater precision to screening and health optimisation in general practice.

“Working in partnership with experts at The Institute of Cancer Research and The Royal Marsden means we can integrate whole-genome sequencing into screening in primary care with the genetic support that is essential. There is no doubt that primary care is the future setting for whole-genome screening which will be carried out by specially trained practice nurses supported by GPs and consultant geneticists.”

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