Abstract

ASSOCIATION OF DIHYDROPYRIMIDINE DEHYDROGENASE GENE POLYMORPHISM WITH TOXICITY OF 5-FLUROURACIL IN COLORECTAL CANCER IN KHARTOUM STATE

Rayan Ahmed Yousif Mohamed Ali*, Hind Mohamed Abushama

Abstract

5-Fluorouracil (5-FU) remains one of the most frequently prescribed chemotherapeutic drugs for the treatment of colorectal cancer. The 5- fluorouracil pathway is affected by a number of genes that are known to be polymorphic, one of them is dihydropyrimidine dehydrogenase (DPYD) gene. The present study is one of the leading study to document the genotype and allele frequency of DPYD IVS14+1G>A polymorphism among Sudanese individuals diagnosed with colorectal cancer and receiving 5-FU chemotherapy compared to healthy controls. The wild and mutant types of DPYD gene were detected and a possible association with 5-FU toxicity and ABO blood groups has been evaluated. A PCR-RFLP designed to detect DPYD IVS14+1G>A polymorphism was used. Results have shown the frequency of cases to controls with DPYD IVS14+1G>A polymorphism was (37%:25% respectively), while cases to controls with wild type was (63%:75% respectively). There is a significant association between male and female cases with heterozygous G/A genotype and carriers of blood group O and A respectively. There was no significant association between DPYD IVS14+1G>A polymorphism and neutropenia toxicity. Significant association were found between DPYD IVS14+1G>A polymorphism and 5-FU GI toxicity. The experienced 5-FU toxicities by cases in the present study emphasize the importance to incorporate DPYD gene polymorphism assessment test to all colorectal cancer patients who candidate to use 5-FU to enhance the prediction of 5-FU toxicity. This could be added to DPYD IVS14+1G>A polymorphism screening with the PCR-RFLP technique is simple and inexpensive (Approximately 8-10$).

Keywords: DPYD IVS14+1G>A, 5-flurouracil, Toxicity, Colorectal cancer, Khartoum state.