NHS Genomics Hub Tests for New Anti-Cancer Drug Variant

Routine genetic testing to guide use of chemotherapy has incorporated a new “African” gene variant which could potentially help save the lives of Black and ethnic minority cancer patients.

Since the test went live in September 2025 at Manchester University NHS Foundation Trust’s North West Genomic Laboratory Hub (GLH), three patients of African ancestry at risk of adverse side effects and toxicity resulting from chemotherapy drugs responded positively following tests.

Until last year, in the UK, genetic tests were carried out which only sought to identify four main DPYD variants, typically found in the DNA of White Europeans.  Further tests to include the fifth variant are now underway at six other Genomic Hubs.

Deficiency of dihydropyrimidine dehydrogenase (DPD), an enzyme produced in the body to break down a particular type of chemotherapy known as fluoropyrimidines, can lead to an insufficient breakdown of the drug leading to severe side effects affecting the bone marrow, bowel and skin, and can cause occasional fatalities.

The test is delivered from the Liverpool site of the North West GLH which provides DPYD genetic testing across the North West of England for more than 450 patients each month. It was one of the first genomic NHS laboratories in England to start routine, clinical testing for this fifth DPYD genomic variant.

The results are particularly significant as data/research for many cancer patients of non-European ancestry would not be routinely captured or reported as having a reaction to fluoropyrimidine chemotherapy.

Until now, other variants, more commonly found in diverse, ethnic groups, and which effect the breakdown of fluoropyrimidine chemotherapy, were not tested across the NHS, limiting outcomes and exacerbating ethnic health inequalities across cancer care.

Inclusion of the fifth variant, known as c.557A>G, in routine testing means that in the North West, three patients, aged 47, 59 and 76, are now receiving altered starting doses of chemotherapy, reducing their risks of experiencing potentially fatal adverse drug reactions.

In 2024, the NHS Race and Health Observatory in partnership with the University of Liverpool published a systematic review of research findings which highlighted limitations in testing for ethnic gene variants in anti-cancer drug treatments used across the NHS.

Dr Vivek Misra, Consultant Clinical Oncologist, The Christie NHS Trust Hospital, Manchester, said:

“It is really great that the North West GLH was able to pick up this mutation. I have started the patient’s treatment with a dose reduction which I otherwise would not have done and she could have experienced more toxicity by being on the full dose of capecitabine.”

Professor Habib Naqvi, Chief Executive, NHS Race and Health Observatory, said:

“Our work has led to a groundbreaking outcome in the use of chemotherapy, which is already having a positive impact on patient’s lives. Genomics and precision medicine are currently at the cutting edge of medical technology, promising a world in which treatments can be more targeted and effective. However, we also know that ethnic minority groups are under-represented in medical research and in genomic biobanks. Research needs to be conducted with diverse populations – only then can medical advances benefit everyone.”

Within the NHS in England, one of the main applications of Pharmacogenomics is to direct fluoropyrimidine-based chemotherapy dosing in patients who have cancers including breast, colorectal and gastric cancer. Up to 40% of the 38,000 patients treated with fluoropyrimidine-based chemotherapy in England each year are at risk of developing an adverse drug reaction (ADR), this may include neutropenia, severe diarrhoea, vomiting, cardiac and neurological complications, and in some cases, death.

Professor Sir Munir Pirmohamed, David Weatherall Chair of Medicine, University of Liverpool, said:

“It is great news for patients that the NHS was able to introduce the c.557A>G variant into the testing panel for DPYD based on our research findings.  This is in keeping with the 10-year NHS plan to prevent serious adverse drug reactions through genomic testing. However, it is important to note that this is the beginning of the journey, rather than the end of journey, as there many other variants in this gene, which need to be evaluated, and implemented into the testing panel.  This will benefit more patients irrespective of their ethnic background.”

Emma Howard, North West Genomic Laboratory Hub Scientific Operational Director, said:

“Genomic testing is continuing to evolve as our understanding of genetic variation improves. By expanding the testing panel, we are taking a practical step towards ensuring cancer treatments are informed by evidence that better reflects the diversity of patients treated across the NHS.”

Patients of African descents can also receive false-negative results if  laboratories only factor European-centric variants which do not include c.557A>G in DPYD panels.

Academic general practitioner, Dr Veline L’Esperance, Senior Clinical Advisor, NHS Race and Health Observatory, said:

“For too long, the genetic diversity of our patients has been rendered invisible by the very tools designed to protect them. This moment represents something rare in healthcare, research translated into policy, and policy translated into practice, with tangible results for patients who have historically been left behind. Including this variant is not simply a technical update; it is proof that when we commit to equity at every stage of the pipeline, from the evidence base through to clinical implementation, we can close gaps that should never have existed. Patients of African ancestry deserve the same standard of safety as everyone else, and now clinicians have the means to deliver it.”