基因多态性与FOLFOX方案治疗胃肠癌敏感性的关系

Relationship between gene polymorphisms and sensitivity to FOLFOX chemotherapy in patients with gastrointestinal cancer

目的研究MTHFR C677T和XRCC1 G28152A基因多态性与接受FOLFOX方案的胃肠癌患者化疗敏感性与毒副反应的关系。方法经FOLFOX方案化疗的进展期胃肠癌48例(22例有临床可观察肿瘤病灶),化疗前抽外周静脉血2 mL,用PCR-RFLP技术检测研究对象的MTHFR C677T和XRCC1 G28152A基因型。化疗两周期后全面评价疗效及毒副反应,并随访观察进展情况。结果 (1)48例胃肠癌患者,MTHFR 677 C/C、C/T、T/T基因型分别为39.6%、37.5%及22.9%。XRCC1 28152 G/G、G/A、A/A基因型分别为52.1%、45.8%及2.1%。22例可观察肿瘤病灶者MTHFR 677 C/C、C/T、T/T基因型疾病控制率分别为14.2%、66.6%和100.0%,T/T基因型明显高于C/C型(P<0.05);XRCC1 28152 G/G、G/A+A/A基因型疾病控制率分别为90.9%、36.4%,差异有统计学意义(P<0.05)。(2)48例患者带有MTHFR677 C/C、C/T、T/T基因型的2年无复发生存率分别为21.1%、36.8%和72.7%,T/T基因型明显高于C/C型(P<0.05);XRCC1 28152 G/G、G/A+A/A基因型2年无复发生存率分别为52.0%和21.7%,差异有统计学意义(P<0.05)。(3)患者接受FOLFOX方案化疗后带有MTHFR 677 C/T、T/T患者恶心/呕吐的发生率(77.8%、81.8%)明显高于C/C基因型患者(26.3%)。XRCC1 28152 G/G、G/A+A/A基因型恶心/呕吐分别为44.0%,78.3%,差异有统计学意义(P<0.05),其余毒副反应与基因型之间差异均无统计学意义(P>0.05)。结论 MTHFR C677T和XRCC1 G28152A基因多态对胃肠癌接受FOLFOX方案化疗疗效与毒性有良好的提示作用。

Objective To evaluate the relationship of the gene polymorphisms of methylenetetrahydrofolate reductase（MTHFR） C677T and X-ray cross complementing group1（XRCC1） G28152A with response to FOLFOX chemotherapy in advanced gastrointestinal cancer.Methods Blood samples were collected from 48 patients with advanced gastrointestinal cancer before treatment.PCR-RFLP was used to determine the genotypes of MTHFR C677T and XRCC1 G28152A polymorphism.All patients received FOLFOX chemotherapy;the therapeutic response and adverse effect were assessed after two cycles.Results The frequencies of MTHFR 677 C/C,C/T and T/T genotype were 39.6%,37.5% and 22.9%;the frequencies of XRCC1 28152 G/G,G/A and A/A genotype were 52.1%,45.8% and 2.1%.In 22 cases whose lesions were clinically measurable,the disease control rates in MTHFR 677 C/C,C/T and T/T genotype were 14.2%,66.6% and 100.0%,respectively（P〈0.05）.The disease control rates in XRCC1 28152 G/G,G/A＋A/A were 90.9% and 36.4%（P〈0.05）.The rates of two-year progression-free survival in patients with MTHFR 677 C/C,C/T and T/T genotype were 21.1%,36.8% and 72.7%,respectively（P〈0.05）;while the rates of two-year progression-free survival in patients with XRCC1 28152 G/G,G/A＋A/A were 52.0% and 21.7%（P〈0.05）.The complication rates of nausea/vomiting in MTHFR 677 T/T and C/T（77.8% and 81.8%） were significantly higher than those in C/C genotypes（P〈0.05）;And nausea/vomiting rate in G/G and G/A＋A/A was 44.0% and 78.3%（P〈0.05）.Conclusion The polymorphisms of MTHFR C677T and XRCC1 G28152A may be of value to predict the efficacy and adverse effect in FOLFOX chemotherapy of gastrointestinal cancer.