Screening for gene variants should be broadened to reduce health inequalities, systematic review concludes

Genetic screening for DPYD gene variants in the UK should be broadened to include variants present in some non-European ancestry groups, a systematic review published in the British Journal of Cancer has concluded.

Variants of the DPYD gene have been associated with a deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme. The DPD enzyme breaks down fluoropyrimidines, a class of drug widely used to treat various types of cancer.

The review — undertaken by the NHS Race and Health Observatory in partnership with the University of Liverpool — looked at 32 studies published between 1998 and 2022, which covered 53 DPYD genetic variants found in patients from 12 countries and 5 ethnic groups: African American, East Asian, Latin American, Middle Eastern, and South Asian.

“Our analysis shows that three of the four variants are also important in South Asian, East Asian and Middle Eastern individuals,” the paper said.

“From the evidence gathered, and based on practice elsewhere in the world, we feel that it would be important to extend DPYD genetic testing in the UK NHS to include the c.557A>G variant, which has been identified in individuals of African ancestry.

“The other variants described in this systematic review need further evaluation for incorporation into the testing pathways either in the UK or elsewhere including other multi-ethnic countries like the EU, USA and Canada, where non-Europeans represent 10–15%, 24.5%, 10.8% of the population, respectively.”

In 2020, NHS England commissioned routine testing for DPD deficiency risk, which looks for four DPYD variants.

A policy statement published at the time said: “The majority of evidence linked to these four DPYD variants is in white Caucasian populations.

“The frequency of various DPYD variants and associated phenotypes varies significantly between different ethnic groups and this should be considered in clinical decision-making”.

In a statement published on 26 July 2024, study author Sir Munir Pirmohamed, NHS chair of pharmacogenetics at the 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.”

Commenting on the findings, Mahendra Patel, director of the Centre for Research Equity at the University of Oxford, said: “There has been under-representation in clinical research and trials from, particularly, black and ethnic minority communities for many years: not just in the UK but the [United States] as well.

“That people who are being affected are not being recruited into studies and clinical trials is something that we really need to address and work towards.

“You are increasing inequality by not having research equity.”