Status: Open
Specialty: Multiple ()
Date Opened: 19/Oct/2023
Planned Close Date: 30/Apr/2026
Sponsor: University of Liverpool
Principal Investigator: Dr Moon
Study Title: Molecular genetics of adverse drug reactions: from candidate genes to genome wide association studies
Our study aims to recruit participants who have experienced an Adverse Drug Reaction (ADR) to any drug. As part of the study, we will collect a small blood or saliva sample from the participants to conduct genetic analysis. One specific ADR we are investigating is caused by a deficiency in the enzyme Dihydropyrimidine dehydrogenase (DPD), which is responsible for breaking down anticancer drugs such as 5-fluorouracil (5FU), capecitabine, and tegafur.
A deficiency of this enzyme, either complete or partial, can result in the inadequate breakdown of these drugs, leading to increased toxicity and potential harm to the bone marrow. In some cases, this has even resulted in severe toxicity and death in patients receiving these drugs. However, if a patient is found to have a genetic deficiency in DPD, a dose alteration may be possible, reducing the likelihood of bone marrow suppression and other toxicities associated with the treatment.
Currently, prior to prescribing 5FU, all patients in the NHS undergo routine testing for four variants of the DPD gene, and doses are adjusted accordingly to prevent toxicity. The purpose of our research is to identify any additional variants across diverse ancestral populations
To achieve this, samples are tested using genotyping methods. While the four variants routinely tested for are largely associated with European populations, there is limited literature on DPD deficiency in non-European populations. As a result, non-European populations are typically treated as wild type and prescribed the conventional dose, which puts them at higher risk of toxicity. By testing for variants in non-European populations, we may be able to identify new variants that affect these populations.
Patient willing to take part
18 years of age or over
Diagnosed with Adverse Drug Reaction (ADR).
ADR’s can affect almost any organ system: for the purpose of this project, the patients to be recruited in general will have had one or more of these reactions:
(A) Generalised hypersensitivity reactions (characterised by fever, skin rash and eosinophilia);
(B) Skin reactions which required drug discontinuation;
(C) Hepatotoxicity;
(D) Haematological toxicity including agranulocytosis and aplastic anaemia;
(E) Pneumonitis;
(F) Metabolic abnormalities such as lipodystrophy and insulin resistance
(G) Retinal problems including retinopathy and visual field constriction.
(H) Bleeding from anticoagulants
(I) Muscle toxicity associated with drugs such as statins
(J) Renal toxicity (including interstitial nephritis, tubular dysfunction, acute renal failure)
(K) Extrapyramidal reactions from antipsychotics
(L) Depression caused by drugs such as isotretinoin.
(M) Osteonecrosis of the jaw associated with bisphosphonates.
(N) Anaphylaxis to anaesthetics
(O)Anaphylaxis to chemotherapy
(P)Chemotherapy induced peripheral neuropathy
(Q) Lung toxicity associated with bleomycin <
(R) Hodgkins lymphoma associated with bleomycin
(S) Angiotensin-convertin enzyme (ACE) inhibitor induced angioedema
Written informed consent obtained
If patient lacks capacity to consent then a personal consultee or a nominated consultee will be approached (Only applies to NHS sites in England, which are set up for this process)
Patient unwilling to take part
Unable to obtain written informed consent
Patient is, in the opinion of the Investigator, not suitable to participate in the study
Patient on additional trial and has been deemed non-eligible for trial by Principle Investigator
Patient does not meet case criteria
Research Nurse: Hilary Thatcher
Administrators: research.oncology@mbht.nhs.uk
Link to EDGE