Predictive role of MMP-2 genetic variants on severe hematologic toxicity of NSCLC patients treated with first-line, platinum-based chemotherapy

Purpose: MMP-2 plays an important role in hematopoietic recovery after chemotherapy-induced myelosuppression. In this study, we investigated the association between MMP-2 SNPs and the incidence of adverse hemtologic events in advanced NSCLC patients treated with platinum-based chemotherapy. Methods: A retrospective pharmacogenetic association study was performed in 1004 Chinese patients with advanced NSCLC receiving platinum-based regimens (including NP, GP, TC, TP). Information about grade 3 or 4 hematologic toxicity (neutropenia, anemia, thrombocytopenia) was available. 16 tag SNPs of MMP-2 were assessed. Results: There were 6 SNPs significantly associated with risk of grade 3 or 4 hematologic toxicity in platinum-based treatment. The variant homozygotes of rs12934241 exhibited the most significant influence on the occurrence of severe neutropenia ( P =9.3×10 -5 ). In stratification analysis by chemotherapy regiments, we found the greates correlations in patients receiving cisplatin-gemcitabine: 7 polymorphisms were found be associated with severe neutropenia, especially rs12934241 (2.9% for C/C v 66.7% for T/T; P =4.9×10 -5 ). Consistent results were found in MMP-2 haplotype analyses. In patients receiving cisplatin-navelbine, we also observed 6 SNPs significantly associated with grade 3 or 4 hemtologic toxicity. However, in cisplatin/carboplatin-paclitaxel treatment groups, no correlation with such toxicity was found. Conclusions: Our study, for the first time, provides evidence for the predictive role of MMP-2 polymorphisms on severe chemotherapy-related hematologic toxicity variability among platinum-treated advanced NSCLC Chinese patients.