MTHFR 677位基因多态性与大剂量MTX联合甲酰四氢叶酸钙治疗骨肉瘤关系的临床研究

目的研究骨肉瘤患者人群中MTHFR677的基因突变的频率分布，比较MTHFR677位基因突变与大剂量MTX联合甲酰四氢叶酸钙治疗骨肉瘤的临床疗效以及毒副反应的发生率的关系。方法选取我院住院治疗的骨肉瘤患者210例，采用RT-PCR方法检测分析MTHFR677位点基因突变在骨肉瘤中的分布频率，同时分析不同MTHFR677基因型患者的临床疗效与毒副反应。结果210例患者中，MTHFR677位CC野生型患者115例，频率为54．8％；677位CT型患者63例。突变频率为30％；677位TT型患者32例，突变频率为15．2％。MTHFR677位基因型不同的三组患者，肿瘤细胞坏死率差异无统计学意义（P〉0．05）。5年无瘤生存率差异无统计学意义（P〉0．05）。MTHFR677位发生CT或TT突变的患者，血尿发生比例明显升高，差异有统计学意义（P〈0．05）。结论大剂量的MTX联合甲酰四氢叶酸钙治疗骨肉瘤患者，不同MTHFR677位基因型患者出现肾毒副反应发生率有差异，尤其是MTFHR677位发生突变的患者出现肾脏毒副反应的发生率高于野生型。

Clinical investigation on the relationship between MTHFR 677 genotype and high dose MTX combined with calcium leucovorin treatment for the patients with osteosarcoma

Objective To investigate the frequency of MTHFR 677 genotype among patients with osteosarcoma. The relationship between MTHFR 677 mutation and clinical efficacy and adverse drug reaction of the high dose MTX combined with calcium leucovorin treatment for the patients with osteosarcoma. Method 210 blood samples were collected and MTHFR 677 was genotyped by RTPCR. The clinical efficacy and adverse drug reaction were compared among groups with different MTHFR677 genotype. Results The frequency of MTHFR 677 CC, CT and TF were 54.8%, 30% and 15.2% respectively. There was no statistical difference on the tumor cell necrosis rate among the groups with different genotype （P〉0.05）. The frequency of Hematuria were significant higher in the CT and TI＂ groups than that of CC group （P〈0.05）. Conclusion The frequency of renal adverse reaction among the different genotype groups treated by MTX combined with calcium leucovorin was significantly different. The frequency of renal adverse reaction in the group with MTHFR 677 mutation was significantly higher than that of wide type group.