150P - Prevalence of DPYD variants in 1478 cancer patients receiving fluoropyrimidine chemotherapy: A real-world data analysis

Background

The DPYD gene encodes the enzyme dihydropyrimidine dehydrogenase (DPD), crucial for metabolizing chemotherapeutic agents like capecitabine, 5-fluorouracil (5-FU), and tegafur. Variants in DPYD can lead to increased chemotherapy toxicity. Despite routine DPYD testing, data on variant prevalence across different tumours, ethnic groups, and the impact of social deprivation on testing access are limited.

Methods

We collected data from 1478 patients referred to Nottingham University Hospitals (01 Dec 2021-31 Dec 2023) for 5-FU, capecitabine, or tegafur chemotherapy, including demographics, ethnicity, tumour type, and DPYD test results. Statistical analysis was performed using SPSS (v28.0). We integrated DPYD test results with the Index of Multiple Deprivation (IMD) data, recorded per Lower Super Output Area (LSOA), to analyze testing rates by social deprivation through choropleth mapping and statistical variance testing.

Results

Mean age was 62.69 years (46.7% male, 53.3% female). Overall DPYD variant prevalence was 7.0%. Variability was noted across tumour types: 7.9% in colorectal, 6.2% in breast, 7.2% in hepato-pancreatico-biliary, and 5.8% in upper gastrointestinal cancers. Other tumour types showed 3.9%. DPYD variant rates by ethnicity were 5.0% in Afro-Caribbean, 6.7% in Asian, and 7.4% in Caucasian patients. Ethnicity was unknown in 182 patients with a 5.5% variant rate. The most common variant was c.1129-5923C>G (HapB3) (75.7%), followed by c.1905+1G>A (DPYD2A) (13.6%) and c.2846A>T (D949V) (8.7%). Homozygous c.1129-5923C>G (HapB3) and c.1679T>G (DPYD*13) were each observed in 1.0%. Social deprivation analysis showed no significant differences in DPYD testing rates between the most and least deprived LSOAs (Mann-Whitney test p-value=0.74).

Conclusions

DPYD variants are present in 7% of patients eligible for 5-FU, capecitabine, or tegafur chemotherapy in our cohort. Caucasian and colorectal cancer patients have the highest variant rates. No variation in DPYD testing was observed based on social deprivation.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

S. Madhusudan.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.