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目的:观察RRM1亚基基因多态性对预测非小细胞肺癌(non-small cell lung cancer,NSCLC)患者以铂类为基础的化疗方案的敏感性和化疗毒性的临床价值。方法:用PCR-RFLP技术检测214例NSCLC患者RRM1启动子基因型。所有患者均经以铂类为基础的化疗方案治疗。结果:214例NSCLC病例中,RR37C/C、C/A和A/A基因型分别为116例(54.46%)、87例(40.85%)和10例(4.69%),化疗有效率分别为44.83%(52/116)、45.98%(40/87)和30.00%(3/10),差异无统计学意义(P=0.629),调整OR值为0.68(95%CI:0.16～2.85);RR524C/C、C/T和T/T基因型分别为25例(11.68%)、89例(41.59%)和100例(46.73%),化疗有效率分别为24.00%(6/25)、51.69%(46/87)和43.00%(43/100),差异有统计学意义(P=0.046),C/T+T/T基因组的有效率显著高于C/C基因组,P=0.008。携带RR524T等位基因型者的化疗敏感性是RR524C/C基因型患者的2.7倍,调整OR=2.70(95%CI为0.98～7.41)。化疗后总有效率(完全缓解+部分缓解)为44.4%。RR37A/A基因型患者化疗相关的血转氨酶升高显著高于C/C、C/A基因型者,P=0.02。结论:RRM1基因RR524基因型多态性可影响以铂类为基础的化疗方案治疗肺癌的敏感性,RRM1基因检测对指导NSCLC的化疗、预测疗效具有较高的临床价值。
Objective: To investigate the clinical value of RRM1 subunit gene polymorphism in predicting the sensitivity and chemotherapeutic toxicity of platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC). Methods: PCR-RFLP was used to detect the RRM1 promoter genotype in 214 patients with NSCLC. All patients were treated with a platinum-based chemotherapy regimen. Results: The genotypes of RR37C / C, C / A and A / A were 116 cases (54.46%), 87 cases (40.85%) and 10 cases (4.69%) in 214 NSCLC cases respectively. The effective rates of chemotherapy were 44.83 (P = 0.629). The adjusted OR was 0.68 (95% CI: 0.16-2.85); RR524C C, C / T and T / T genotypes were 25 cases (11.68%), 89 cases (41.59%) and 100 cases (46.73%) respectively. The effective rates of chemotherapy were 24.00% (6/25) and 51.69% (46/87) and 43.00% (43/100) respectively. The difference was statistically significant (P = 0.046). The efficiency of C / T + T / T genome was significantly higher than that of C / C genome, P = 0.008. The chemosensitivity to RR524T allele was 2.7-fold greater than that of patients with RR524C / C genotype, adjusted for OR = 2.70 (95% CI 0.98 to 7.41). After chemotherapy, the total effective rate (complete remission + partial remission) was 44.4%. Patients with RR37A / A genotype had higher serum ALT levels than C / C and C / A genotypes (P = 0.02). Conclusion: The RR524 genotype polymorphism of RRM1 gene may affect the sensitivity of platinum-based chemotherapy in the treatment of lung cancer. RRM1 gene detection has a high clinical value in guiding the chemotherapy and prognosis of NSCLC.