Impact of dihydropyrimidine dehydrogenase deficiency on oxidative stress index induced by 5-fluorouracil therapy in patients with stage-III colorectal cancer patients

Abstract

Background & objective: To the best of our knowledge, no previous studies have examined the valuation of oxidative stress levels in colorectal cancer patients with dehydropyrimidine dehydrogenase (DPD) deficiency who are receiving 5-fluorouracil chemotherapy. The aim of this study is to determine the oxidative stress index (OSI) in stage III colorectal cancer patients with DPD deficiency who are receiving 5-fluorouracil (5-FU) chemotherapy.

Methods: This study comprised 164 male patients with stage III colorectal cancer, all of whom got adjuvant treatment containing of a single cycle of 5-fluorouracil (5-FU). Participants were categorized according to their DPD levels into two groups: 82 males with DPD deficiency and 82 males without DPD deficiency. Multiple regression analyses were carried out to evaluate the OSI and its related elements after adjusting for potential confounders, and receiver operating characteristic (ROC) curve analysis was conduct to evaluate the diagnostic performance of OSI.

Results: The OSI was expressively higher in DPD-deficient patients in comparison with non-DPD-deficient patients (P < 0.001). OSI exhibited a significant negative correlation with DPD levels (r = –0.674, P < 0.001) and white blood cell (WBC) count (r = –0.570, P < 0.001). In multiple regression analysis, DPD level was independently related with OSI (P < 0.001). Additionally, receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic performance of OSI, with an area under the curve (AUC) of 0.989 (95% CI: 0.979–0.999, P < 0.001).

Conclusions: A strong relationship was observed between DPD deficiency and severe systemic oxidative stress in colorectal cancer patients receiving 5-FU chemotherapy.