The frequency of DPYD*2A and MTHFR C677T single nucleotide polymorphisms related to Capecitabine toxicity in Colorectal Cancer patients from Sulaymaniyah, Iraq

Abstract
Purpose
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Capecitabine, an oral prodrug which primarily used in CRC chemotherapy. Variations in the enzymes dihydropyrimidine dehydrogenase DPYD (DPYD*2A) and methylenetetrahydrofolate reductase MTHFR (MTHFR C677T) genes can result in severe capecitabine-related toxicity in CRC patients. The main purpose of this study was to analyse the frequency of these two important polymorphisms in Iraqi population to complete their global map.
Methods
Blood samples were collected from 170 individuals for MTHFR genotyping, and from 422 individuals for DPYD*2A genotyping, all from the Sulaymaniyah population in Iraq. Genomic DNA was isolated from whole blood, and the tetra-ARMS PCR assays were developed to detect MTHFR C677T and DPYD*2A variants.
Results
The genotype distribution for MTHFR C677T among the 170 participants was as follows: C*/C*: 52. 4%, C*/T*: 37%, and T*/T*: 10. 6%. The corresponding allele frequencies were C*: 70. 9% and T*: 29. 1%. In contrast, all 422 samples tested for DPYD*2A were homozygous wild genotype, with a mutant allele frequency of 0.0%. These findings were validated by DNA sequencing for a fraction of the samples.
Conclusion
The high prevalence of the MTHFR C677T polymorphism in the Sulaymaniyah population of Iraq, highlighting the necessity of its genetic screening before initiating capecitabine therapy in CRC patients. Although the DPYD*2A variant was not observed, pre-treatment genotyping remains advisable due to its potential clinical impact. Furthermore, the tetra-ARMS PCR represents a rapid and cost-effective method for SNP genotyping in clinical settings.