Yuan Zhi-Jun, Zhou Wen-Wu, Liu Wei, Wu Bai-Ping, Zhao Jin, Wu Wei, He Yi, Yang Shuo, Su Jing, Luo Yi
Medical Department of Veteran Cadre, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China E-mail :
Asian Pac J Cancer Prev. 2015;16(10):4347-51. doi: 10.7314/apjcp.2015.16.10.4347.
Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1) were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) were correlated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivity and clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatin regimens.
DNA sequencing was used to evaluate genetic polymorphisms of GSTP1 Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinical response was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessed by 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents).
There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequency distribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive group had higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the joint detection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A+high effective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicity showed no correlation with the genotypes between two groups (p>0.05).
Compared with single detection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may be more helpful for patients with NSCLC to receive gemcitabine-cisplatin regimens as the first-line chemotherapy. Especially, genetic polymorphism of RRM1 is more likely to be used as an important biomarker to predict the response and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.
先前的研究表明，谷胱甘肽S-转移酶P1（GSTP1）的基因多态性参与谷胱甘肽代谢，核糖核苷酸还原酶（RRM1）的基因多态性与DNA合成相关。在此，我们探讨了这些多态性对接受吉西他滨-顺铂方案治疗的中国非小细胞肺癌（NSCLC）患者化疗敏感性和临床结局的影响。
采用DNA测序法评估47例接受吉西他滨-顺铂方案治疗的NSCLC患者GSTP1 Ile105Val和RRM1 C37A-T524C的基因多态性。化疗2个周期后根据RECIST标准评估临床反应，并按照1979年WHO标准（化疗药物急性和亚急性毒性分级标准）评估毒性。
GSTP1 Ile105Val多态性的基因型频率分布在敏感组和非敏感组之间无统计学意义（p>0.05）。但对于RRM1 C37A-T524C基因型，敏感组高效基因型比例高于非敏感组（p=0.009）。根据GSTP1 Ile105Val和RRM1 C37A-T524C多态性的联合检测，敏感组A型（A/A+高效基因型）比例显著高于非敏感组（p=0.009）。两组毒性与基因型均无相关性（p>0.05）。
与单独检测GSTP1 Ile105Val或RRM1 C37A-T524C基因多态性相比，两者联合检测可能对NSCLC患者接受吉西他滨-顺铂方案一线化疗更有帮助。特别是，RRM1基因多态性更有可能作为预测NSCLC患者吉西他滨-顺铂联合化疗反应和毒性的重要生物标志物。
