胃癌患者MTHFR C677T基因多态性与SOX化疗方案的疗效及关联性研究

Efficacy and correlation between MTHFRC677Tgene polymorphism and SOX chemotherapy regimen in patients with gastric cancer

目的亚甲基四氢叶酸还原酶基因(methylenetetrahydrofolate reductase,MTFHR)的基因多态性影响肿瘤的易感性,MTHFRC677T多态性与恶性肿瘤5-氟尿嘧啶(5-FU)化疗的预后存在关联性。本研究探讨MTHFR C677T的基因多态性对胃癌根治术后联合奥沙利铂+替吉奥(SOX)方案化疗患者预后的关系以及疗效的影响。方法选取2012-01-01-2016-12-31新疆医科大学附属肿瘤医院就诊并经病理确诊的胃癌患者85例。根据C677T基因多态性将患者分为CC组和CT/TT组,分析2组患者的性别、年龄、TNM分期、淋巴结转移情况、分化情况及生存资料。采用生存分析比较不同MTHFRC677T基因型患者基于SOX方案化疗后复发及生存情况。结果85例胃癌患者中CC基因型为22.35%(19/85),CT基因型为51.77%(44/85),TT基因型为25.88%(22/85)。符合Hardy-Weinberg平衡定律,χ^2=0.09,P>0.05。CC基因型患者中位无复发生存期(recurrence free survival,RFS)为21.33个月,CT或TT基因型患者中位RFS为28.77个月,χ^2=4.58,P=0.03。CC基因型患者中位总生存期(overall survival,OS)为27.57个月,CT或TT基因型患者中位OS为42.53个月,χ^2=5.52,P=0.02。Cox比例风险回归模型显示,MTFHR基因型CC(OR=1.263,95%CI为1.105~1.444)和淋巴结转移(OR=1.560,95%CI为1.285~1.894)是影响患者RFS的独立危险因素;MTFHR基因型CC(OR=1.496,95%CI为1.134~1.975)和淋巴结转移(OR=2.265,95%CI为1.196~4.289)是影响患者OS的独立危险因素。结论MTHFRC677T基因多态性影响胃癌根治术后联合SOX化疗患者的预后,基因型CC是其复发与死亡的独立危险因素。

OBJECTIVE Gene polymorphism of methylenetetrahydrofolate reductase gene(MTFHR)can affect tumor susceptibility.MTHFR C677Tpolymorphism is correlated with prognosis of 5-Fu chemotherapy in malignant tumors.This study aimed to study the gene polymorphism of MTFHR C677Tthe relationship between sexuality and prognosis of patients with gastric cancer combined with SOX chemotherapy,and to explore the effect of MTFHR C677T gene polymorphism on the efficacy of SOX chemotherapy in gastric cancer patients.METHODS A total of 85patients with gastric cancer who were diagnosed by the hospital pathological diagnosis and diagnosed by the hospital pathology from 2012-01-01-2016-12-31were categorized into the CC677and CT/TT groups.The gender,age,TNM stage,lymph node metastasis,differentiation,and survival data of the two groups were analyzed.Survival analysis was used to compare the recurrence and survival of patients with different MTFHRC677Tgenotypes based on SOX chemotherapy.RESULTS Of the 85gastric cancer patients,22.35%(19/85)patients carried the CC genotype,51.77%(44/85)patients carried the CT genotype,and 25.88%(22/85)patients carried the TT genotype;This result was consistent with the Hardy-Weinberg equilibrium law(χ2=0.09,P>0.05);The median RFS with CC gene was 21.33months,and the median RFS of patients with CT gene or TT gene was 28.77months(χ2=4.58,P=0.03);the median OS with CCgene was 27.57months.The median OS of patients with CT gene or TT gene was 42.53months(χ2=5.52,P=0.02);Cox proportional hazard regression model showed that MTFHRgenotype CC was an independent risk factor affecting RFS in patients,with an ORvalue of 1.263(95%CI=1.105-1.444),and lymph node metastasis was also an independent risk factor affecting RFS in patients 95%CI=1.285-1.894);At the same time,MTFHRgenotype CC was an independent risk factor that affected the OSof patients.The ORvalue was 1.496(95%CI=1.134-1.975).Lymph node metastasis also an independent risk factor that affected the OSof patients.The ORvalue was 2.265(95%CI=1.196-4.289).CONCLUSION The MTFHR C677Tgene polymorphism may affects the efficacy of gastric cancer which is treated with SOX-based chemotherapy,and genotype CCis independent risk factor influencing recurrence and death.