GSTP1遗传多态性对铂类化疗敏感性的影响

研究谷胱甘肽-S-转移酶P1（glutathione S-transferases P1，GSTP1）基因第105位点的遗传多态性与恶性肿瘤患者对铂类药物化疗敏感性的关系。方法：收集50例经病理确诊且CT扫描证实有可测量病灶并接受以顺铂为主的化疗的恶性肿瘤患者，于化疗前抽取外周静脉血，采用基因测序的方法对GSTP1基因第105位点的单核苷酸多态性（single nucleotide polymorphisms，SNPs）进行检测，观察这些患者经2～4个周期化疗后的疗效，分析各基因分型与铂类药物化疗敏感性的关系。结果：GSTP1基因第105位点基因型的分布与病种无关（P>0.05）。携带GSTP1基因第105位密码子的Ile/Ile、Ile/Val和Val/Val 3种基因型的患者对铂类药物化疗有效率分别为20.0%、36.4%和87.5%，携带纯合突变型Ⅴal/Ⅴal基因分型的患者的敏感性明显高于携带另外2种基因分型的患者（P<0.05）。结论：GSTP1基因单核苷酸多态性可能与铂类药物化疗敏感性相关。

Effect of GSTP1 Genetic Polymorphism on Sensitivity of Platinum- Based Chemotherapy

To investigate the relationship between genetic polymorphism in 105 codons of the glutathione S-transferase P1 ( GSTP1 ) gene and patient sensitivity to platinum-based chemotherapy. Method: A total of 50 cancer patients were enrolled in our study, which were confirmed by pathologic diagnosis and CT scanning to have measurable lesions and then subjected to platinum-based chemotherapy. Peripheral blood was obtained before the therapy, and direct sequencing was performed to detect single nucleotide polymorphisms ( SNPs ) in the 105 codons of GSTP1 in peripheral blood. The clinical responses of these patients after 2 to 4 cycles of chemotherapy were observed. The relationship between SNPs of the GSTP1 gene and clinical responses was analyzed. Results: No correlation was found between the distribution of GSTP1 genotypes and different cancers ( P > 0.05 ). The response rates to chemotherapy in patients with the Ile/Ile, Ile/Val, and Val/Val genotypes in the 105 GSTP1 codons were 20.0%, 36.4% and 87.5%, respectively. The response rate was higher in the patients with the homozygous Val/Val mutant genotype than in those with the Ile/Ile or Ile/Val genotypes ( P < 0.05 ). Conclusion: Single nucleotide polymorphisms of the GSTP1 gene may be associated with sensitivity to platinum-based chemotherapy.