RRM1基因多态性与非小细胞肺癌患者血清铂类化疗敏感的相关性分析

Polymorphisms in RRM1 gene and sensitivity to platin based chemotherapy in non-small cell lung cancer patients

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 relationship between polymorphisms of RRM1 gene and sensitivity to platin based chemotherapy in non-small cell cancer patents. METHODS：A total of 214 patients with histological confirmed non-small cell lung cancer were analyzed. PCR-RFLP was employed to determine the promote genotypes of RRM1. All the patients were treated with platin based chemotherapy. RESULS：Among all the cases,the numbers of RR37C/C,C/A and A/A genotypes were 116（54.46%）,87（40.85%） and 10（4.69%） respectively; the numbers of RR524 C/C,C/T and T/T genotypes were 25（11.68%）,89（41.59%） and 100（46.73%） respectively. The overall response rate of chemotherapy （CR＋PR） was 44.4%. The patients＇ response rates of chemotherapy with RR37C/C,C/A and A/A genotypes were 44.83% （52/116）,45.98%（40/87） and 30.00%（3/10） respectively. There was no statistically significant difference （P=0.629）. OR was 0.68 （95%CI：0.16-2.85）. The response rates to therapy among the patients with RR524C/C,C/T and T/T genotypes were 24.00%（6/25）,51.69%（46/87） and 43.00%（43/100） respectively,with a statistically significant difference （P=0.046）. Further analysis showed that the response rates of patients with RR524 C/T and T/T genotype were significantly higher than those with RR524 C/C genotype （P=0.008）,and adjusted OR=2.70（95%CI：0.98-7.41）. Compared with RR524C/C allele,the patients with RR524T allele had a 2.7-fold sensitivity to platinum-based chemotherapy. The incidence rate of increased ALT in RR37A/A genotype was significantly higher than in C/C and C/A genotypes （P=0.02）. CONCLUSIONS：The polymorphisms of RR524CT are associatated with the sensitivity to platin based chemotherapy in non-small cell lung cancer patients. The detection of RRM1 genotypes may indicate the sensitivity of NSCLC patients and is of value as the guideline of the therapy to platinum based chemotherapy.