Review to explore cancer drug limitations due to ethnic gene variations

Wider genetic testing could save lives, reduce costs and help thousands of Black, Asian and ethnic minority patients at risk of severe side effects resulting from chemotherapy drugs.

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

Historically, the majority of genetic tests used in the NHS and worldwide centre on DNA profiles found in White European populations, limiting optimal effectiveness and outcomes for people of Black, Asian, and other ethnic minority groups.

A deficiency of dihydropyrimidine dehydrogenase (DPD), an enzyme produced in the body to break down particular anticancer drugs, fluoropyrimidines, can lead to an insufficient breakdown of the drug leading to severe side effects affecting the bone marrow, bowel and skin, which in some cases can cause death.

As part of the initial two-year research project, concluding in 2026, researchers found 32 studies, published between 1998 and 2022, involving DPYD gene variants linked with severe side effects from anti-cancer fluoropyrimidine based drugs in Black and other ethnic minority populations.

Currently the UK tests for four DPYD variants, typically found in White Europeans.  The researchers found 53 additional DPYD variants in patients from 12 countries from five ethnic groups: African American, East Asian, Latin American, Middle Eastern, and South Asian.

The results of this study have recently been published in the British Journal of Cancer.

Professor Habib Naqvi, chief executive, NHS Race and Health Observatory, said:

“There is a duty to ensure every patient has access to the best available treatment when they are unwell. It’s therefore important that there is no unwarranted racial bias in how people’s genes affect individual responses to medications. And yet we know that genetic tests used in the NHS are mainly linked to DNA profiles found in White European populations – potentially exacerbating ethnic health inequalities. The innovative work we are undertaking with colleagues at the University of Liverpool will help to tackle this long-standing challenge in healthcare.”

The Observatory and researchers from the Wolfson Centre for Personalised Medicine, University of Liverpool, are calling for the extension of DPYD genetic testing. A further recommendation for genetic testing for a variant found in those from African backgrounds is now under NHS review for potential inclusion in the National Genomic Test Directory.

Professor Sir Munir Pirmohamed, Institute of Systems, Molecular and Integrative Biology (ISMIB), University of Liverpool, said:

“We have been fantastically successful in implementing DPYD genetic testing in the UK, with over 38,000 tests carried out annually in England.  However, this should not be regarded as the end of the journey but just the beginning.  We always need to make sure we are not exacerbating health inequalities – this was the reason for our systematic analysis of the global literature, which has highlighted the need to include a specific variant which is found in people of African ancestry. Evaluation and continual refinement of genetic testing is going to be important throughout the life cycle of any test to ensure that the benefits are optimised for the whole population.”

In October 2020, the Medicines and Healthcare products Regulatory Agency (MHRA), recommended DPD testing before prescribing fluoropyrimidine drugs. In November 2020, the NHS implemented DYPD genetic testing as a pre-treatment screening test prior to using fluoropyrimidine based therapies. This is one of the first pharmacogenomic tests to be applied nationally in the UK.

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

“This work emphasises the need for continued efforts to ensure the National Genomic Test Directory provides equitable genetic testing to all patients for whom it would be of clinical benefit. In instances where genetic data from the UK remain limited due to poor representation of Black and ethnic minority people, it is important to review the literature globally to ensure we are not worsening ethnic health disparities.”