Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer


Background: Previous studies showed that genetic polymorphisms of glutathione S-transferase P1 (GSTP1)were involved in glutathione metabolism and genetic polymorphisms of ribonucleotide reductase (RRM1) werecorrelated with DNA synthesis. Here we explored the effects of these polymorphisms on the chemosensitivityand clinical outcome in Chinese non-small cell lung cancer (NSCLC) patients treated with gemcitabine-cisplatinregimens. Materials and
Methods: DNA sequencing was used to evaluate genetic polymorphisms of GSTP1Ile105Val and RRM1 C37A-T524C in 47 NSCLC patients treated with gemcitabine-cisplatin regimens. Clinicalresponse was evaluated according to RECIST criteria after 2 cycles of chemotherapy and toxicity was assessedby 1979 WHO criteria (acute and subacute toxicity graduation criteria in chemotherapeutic agents).
Results:There was no statistical significance between sensitive and non-sensitive groups regarding the genotype frequencydistribution of GSTP1 Ile105Val polymorphism (p>0.05). But for RRM1 C37A-T524C genotype, sensitive grouphad higher proportion of high effective genotype than non-sensitive group (p=0.009). And according to the jointdetection of GSTP1 Ile105Val and RRM1 C37A-T524C polymorphisms, the proportion of type A (A/A + higheffective genotype) was significantly higher in sensitive group than in non-sensitive group (p=0.009). Toxicityshowed no correlation with the genotypes between two groups (p>0.05).
Conclusions: Compared with singledetection of genetic polymorphisms of GSTP1 Ile105Val or RRM1 C37A-T524C, joint detection of both may bemore 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 theresponse and toxicity of gemcitabine-cisplatin combination chemotherapy in NSCLC.