目的探讨CYP3A5、MDR1和COX-2单核苷酸多态性是否与长春瑞滨、铂类药物对晚期非小细胞肺癌(NSCLC)化疔疗效有关。方法对69例采用长春瑞滨、铂类方案化疗的晚期NSCLC患者(中国汉族)的CYP3A5(*3)、MDR1 21外显子上的2677 G〉T位点、26外显子3435 C〉T位点及其单体型和COX-2启动子区的-1195 G〉A位点用限制内切酶片段多态性一多聚酶链反应(RFLP—PCR)的方法进行基因分型,结合临床化疗效果进行分析,采用卡方检验分析各位点基因型与化疗疗效之间的关系。结果MDR1 3435位点野生纯合子(C/C)患者疗效明显高于杂合子(C/T)和突变纯合子(T/T)患者(P=0.033)。MDR12677位点野生纯合子(G/G)患者疗效明显高于其他基因型患者(P=0.012)。MDR1 2677 G-3435 C单体型患者疗效稍高于其他单体型(P=0.063)。CYP3A5*3位点基因型与长春瑞滨、铂类方案疗效无关。COX-2-1195 G〉A位点野生型(G/G)疗效稍高于其他基因型(P=0.067),但差异无统计学意义。结论MDR13435 C〉T位点基因型和MDR1 2677 G〉A/T位点基因型可以用于预测长春瑞滨、铂类方案对晚期NSCLC患者的疗效。
Objective To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 are associated with the sensitivity of vinorelbineplatinum to NSCLC. Methods The genotypes of CYP3 A5 ( * 3 ) , MDRI (2677G 〉 T at exon 21 and 3435C 〉 T at exon 26 and their haplotypes), cyclooxygenase-2 ( -1195 G 〉 A) were determined by RFLP-PCR and chemotherapy responses were analyzed in 69 non-small-cell lung cancer (NSCLC) Chinese Han patients. They received a combination chemotherapy of vinorelbine-cisplatin. Chi-square test was used to investigate the potential association of genotype with chemotherapy response. OR and 95% CI were calculated. Results The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes ( P = 0. 033 ). The 2677 GG genotype was also associated with a significantly better chemotherapy response compared with the combined 2677 GT and TT genotype(P = 0. 012). Moreover, patients with the 2677 G-3435 C haplotype seemed to have a better response to chemotherapy compared with those with the other haplotypes ( P = 0. 063 ). CYP3A5 * 3 was not likely to correlate with sensitivity of vinorelbine-platinum to NSCLC. Cyclooxygenase-2-1195G 〉 A was likely to have better response to vinorelbine but not statistically significant (P = 0. 067 ). Conclusion Polymorphisms of MDR1 3435C 〉 T and MDR1 2677G 〉 A/T can be used for predicting treatment response to vinorel-bine-cisplatin chemotherapy in NSCLC patients.