Relationship Between MTHFR C677T Gene Polymorphism And Clinical Response Related To Preoperative Methotrexate Chemotherapy In Patients With Osteosarcoma

Objective:To explore the effect of MTHFR(methylenetetrahydrofolate reductase)C677T gene polymorphism in patients with osteosarcoma and related clinical response after HD-MTX(high-dose methotrexate)chemotherapy.Methods:Collect basic clinical data and blood and postoperative tissue samples of 36 patients with osteosarcoma who received 2 courses of HD-MTX neoadjuvant chemotherapy before surgery.Detection of MTHFR C677 T genotype,MTX blood concentration and postoperative tissue necrosis rate,Record HD-MTX-induced chemotherapy-related adverse reactions.Using SPSS23.0statistical software to calculate the odds ratio(OR)and its 95% confidence interval(95%CI)with an unconditional Logistic regression model to indicate the possibility of adverse reactions in individuals with different genotypes;Fisher’s accurate probability was used to compare the 0h,72 h plasma concentration and histological response between different genotypes of MTHFR after HD-MTX chemotherapy.Results: Compared with carriers of CC+CT gene,MTHFRC677 TT gene carriers had 2.7,2.1,1.8 times higher risk of hemoglobin,platelet reduction,and gastrointestinal reactions,but the difference was not statistically significant(all P>0.05).There is no correlation between the various genotypes of MTHFRC677 T and the occurrence of adverse reactions such as leukocyte decline and mucosal damage;Compared with each genotype of MTHFRC677 T,there was no statistical difference between 0 hour ≥ 700umol/L,0 hour <700umol/L,72 hour ≥ 0.2umol/L,72 hour <0.2umol/L and postoperative histological necrosis rate(P>0.05).Conclusion :MTHFRC677T gene mutation may increase the risk of HD-MTX-related adverse reactions,The standardized and individualized treatment should be combined with the MTHFR C677 T genotype and the patient’s individual clinical conditions.