| Objective: To study the relationship between gene polymorphism of dihydropyrimidine dehydrogenase gene(DPYD),5,10-methylenetetrahydrofolate reductase gene(MTHFR)and thymidylate synthase gene(TYMS)in patients with gastrointestinal cancer and the clinicopathological features and their influences on the prognosis of the patients.Methods: Patients’ blood samples or tumor tissue samples were collected.According to an extraction kit,DNA was extracted from the patient’s tumor tissue and blood.Purified plasma samples by column chromatography,high-purity ct DNA can be obtained from magnetic beads.According to the second-generation sequencing principle,genetic testing was performed on tumor cell DNA,blood cell DNA and ct DNA gene fragments,Finally,we got genetic test results by analyzing the genetic data.The date when all patients were diagnosed with colorectal cancer after pathological diagnosis was taken as the start time of follow-up.When the patients died or by December 31,2018 follow-up was completed.Chi-square test or Fisher exact test was used to analyze the relationship between the polymorphism of DPYD,MTHFR and TYMS in patients and the gender,age,depth of invasion,histological grade,Lymph node metastasis,tumor location,ECOG score and first-line evaluation in patients with advanced colorectal cancer.Kaplan-Meier method and Log-rank test were used to analyze the relationship between the number of single gene polymorphism and the number of gene polymorphisms of two or more genes with the overall survival(OS)and progression-free survival(PFS).In single and multiple factors analysis,the COX proportional hazard models were used to assess prognostic factors.P <0.05 was considered statistically significant.Results: This study analyzed 137 patients.There was no statistically significant correlation between DPYD(DPYD*5A and DPYD*9A)gene polymorphism and clinicopathological characteristics.The median OS of patients with DPYD*5A wild type patients was 33.8 months,which was higher than homozygou 16.8 months and heterozygous type 27.7 months(P=0.404).The median PFS of DPYD*5A wild type patients was 8.2 months,which was higher than homozygou 5.4 months and heterozygous type 5.5 months(P=0.068).The median OS of patients with DPYD*9A homozygou mutant patients was 60.8 months,which was higher than heterozygous 55.9 months and wild type 28.2 months(P=0.041).The median PFS of patients with DPYD*9A homozygou type patients was 11.3 months,which was higher than heterozygous 6.9 months and wild type 7.0 months(P=0.201).DPYD*5A gene polymorphism(P=0.049)and DPYD*9A gene polymorphism(P=0.045)were respectively independent risk predictors for the PFS and OS of advanced colorectal cancer patients.There was a statistically significant association between MTHFR gene polymorphism and first-line response(P=0.038),they were independent risk predictors for the PFS of advanced colorectal cancer patients.The median OS of patients with MTHFR wild type was approximately 34.8 months,which was higher than homozygou 27.7 months and heterozygous type 24 months(P=0.637).The median PFS of MTHFR wild type was approximately 8.9 months,which was higher than homozygou 7.5 months and heterozygous type 5.1 months(P=0.048).There was a statistically significant association between TYMS gene polymorphisms and lymph node metastasis in patients(P=0.016).Conclusion: DPYD,MTHFR or TYMS gene polymorphisms were related to the clinicopathological characteristics and prognosis of patients with advanced colorectal cancer.DPYD*5A gene polymorphism was independent risk predictor for the PFS;The patients with DPYD*9A homozygou type have longer overall survival,DPYD*9A gene polymorphism was independent risk predictor for the OS;The patients with MTHFR wild-type have longer progression-free survival,MTHFR gene polymorphism was related to the first-line efficacy of patients,was independent risk predictor for the PFS;TYMS gene polymorphism was related to lymph node metastasis of patients. |
