Analysis of the correlation between dihydropyrimidine dehydrogenase gene polymorphism and clinicopathological features,toxicity and efficacy of chemotherapy in patients with advanced colorectal cancer

Wang Fuhua; Wang Xinyan; Wang Chunyan; Liu Juan; Liu Xiaoling

doi:10.3760/j.issn.1673-4777.2025.07.015

Abstract：Objective To investigate the correlation between dihydropyrimidine dehydrogenase(DPYD)gene polymorphism and clinicopathological features,toxicity and efficacy of chemotherapy in patients with advanced colorectal cancer.Methods A total of 84 patients with advanced colorectal cancer who were admitted to the Department of Gastroenterology,Shanxi Cancer Hospital from April 1,2020 to April 1,2021 were selected.The single nucleotide polymorphism of DPYD gene was genotyped,and the clinicopathological characteristics,toxicity and efficacy of chemotherapy were compared among patients with different genotypes.Results Among the 84 colorectal cancer patients,58 cases(69.0％)had DPYD A1627G wild type AA,2 cases(2.4％)had homozygous mutant GG,and 24 cases(28.6％)had heterozygous mutant AG.The DPYD gene status of colorectal cancer patients was not significantly correlated with gender,age,tumor location,histological grade,and metastasis site(all P＞0.05).The DPYD gene status was significantly correlated with ≥ 3 grade digestive tract reaction and ≥ 3 grade bone marrow suppression(both P＜0.05).There was a significant difference in chemosensitivity between patients with different genotypes(x2=4.719,P=0.046).The progression-free survival(PFS)of patients with DPYD AA was 10.0 months,which was longer than 6.4 months of AG and 5.5 months of GG(x2=6.130,P=0.047).Multivariate analysis showed that,DPYD gene polymorphism(hazard ratio=2.740,95％confidence interval:1.444-5.199,P=0.002)and histological grade(hazard ratio=2.393,95％confidence interval:1.196-4.785,P=0.014)were the independent risk factors for PFS of colorectal cancer patients.Conclusion The DPYD gene status of colorectal cancer patients was not significantly correlated with gender,age,tumor location,histological grade,and metastasis site,and was significantly correlated with≥3 grade digestive tract reaction and ≥ 3 grade bone marrow suppression.There is a certain correlation between DPYD gene polymorphism and chemosensitivity.DPYD AA patients have longer PFS.DPYD gene polymorphism is an independent risk factor for PFS.