Relationship Between Genetic Polymorphisms Of Methylenetetrahydrofolate Reductase And Xeroderma Pigmentosum Group D And Chemosensitivity Of Gastrointestinal Cancer To FOLFOX Chemotherapy

Objective:To evaluate the relationship between the gene polymorphisms of Methylene- tetrahydrofolate reductase (MTHFR) or/and xeroderma pigmentosum group D(XPD)and response to FOLFOX chemotherapy in advanced gastrointestinal cancer.Methods:48 patients with advanced gastrointestinal cancer were divided into adjunctive therapy group(26 cases) and advanced tumor therapy group(22 cases). 2 ml of peripheral blood was extracted from each patient before treatment. PCR-RFLP was used to determine the genotypes of MTHFR C677T polymorphism(C/C,C/T,C/T) and XPD Lys751Gln polymorphism(Lys/Lys,Lys/Gln,Gln/Gln). All of the patients were treated with FOLFOX chemotherapy which was based with 5-Fluorouracil and oxaliplatin, then assessed therapeutic effect and side effect after two cycles.Resluts:Of the 48 cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 39.6%(18/48), 37.5%(19/48) and 22.9%(11/48), while we found two kinds of genotypes of XPD Lys751Gln polymorphism, which included Lys/Lys and Gln/Gln, the frequencies of them were 29.2%(14/48) and 70.8%(34/48), respectively. In advanced tumor therapy group(22 cases), the overal disease control rate to FOLFOX chemotherapy (CR+PR+SD) was 63.6%.The disease control rate to therapy among MTHFR C677T C/C, C/T and T/T genotype patients were14.2%(2/7),66.6%(6/9) and 100%(6/6), respectively. And the disease control rate in patients with T/T genotype was significantly higher than the C/C genotype(P<0.05). The disease control rate to therapy among XPD Lys751Gln Gln/Gln was 42.8%(6/14), while among Lys/Lys was 100%(8/8), which was significantly higher than the Gln/Gln genotype(P<0.05).Of the 48 cases, the rate of progression-free survival in patients with MTHFR C677T C/C, C/T and T/T genotype were 21.1%,22.2% and 63.6%, respectively, and T/T genotype was significantly higher than the C/C and T/T genotype(P<0.05); While the rate of progression-free survival in patients with XPD Lys751Gln Lys/Lys was 35.7%,which was a little more than Gln/Gln genotype(29.4%), but they had no significant difference. The side effect to FOLFOX chemotherapy were mainly nausea/vomiting, diarrhea, myelosuppression, injury of liver and neurotoxicity. The incidence rates of nausea/vomiting in MTHFR C677T T/T,C/T(77.8%,81.8%) or XPD Lys751Gln Lys/Lys(85.7%) were significantly higher than other genotypes(P<0.05).Conclusions:The polymorphisms of MTHFR and XPD may be important factors to predict the efficacy and/or treatment-related toxicity in the FOLFOX chemotherapy of gastrointestinal cancer. It may be helpful to a certain extent for evaluating the prognosis of advanced gastrointestinal cancer patients and/or who receive adjunctive therapy.