Genetic variants of BCL2 gene predict clinical outcomes of non-small-cell lung cancer patients treated with platinum-based chemotherapy in a Chinese population

摘要

Platinum agents induce cancer cell death through BCL2-dependent intrinsic apoptotic pathway and are commonly used as anti-tumor drug. In this study, we evaluated whether single nucleotide polymorphism (SNPs) of BCL2 can affect the overall survival (OS) and progression-free survival (PFS) in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. We genotyped 48 SNPs of BCL2 gene by Illumina Custom Designed Chip in 972 advanced NSCLC patients treated with platinum-based chemotherapy. We evaluated the relationship between genotype/haplotype/diplotype and OS/PFS by COX regression analysis. As a result, five SNPs, rs949037, rs3810027, rs4987739, rs4987726 and rs7226979, were significantly associated with overall survival time in 972 NSCLC patients after platinum-based chemotherapy. rs1381547 and rs8083946 were associated with progression-free survival. As representative, the G allele of rs949037 was associated with longer OS in NSCLC patients with platinum-based chemotherapy. Patients with GG or AG genotype showed a 19.9 months mOS vs AA genotype 14.2 months mOS (HR: 1.38, 95% CI: 1.11-1.72, p=0.004). In further analysis, rs949037 was found to predominantly contribute to the OS of patients with platinum-tubulin-targeting drugs, moreover, the GG genotype of rs949037 showed an 8.5 months longer OS compared with the unfavorable AA genotype (mOS: 21.36 vs 12.83, HR=0.70, 95% CI: 0.52-0.94, p=0.000). To conclude, polymorphisms of BCL2 gene may have an impact on the OS of platinum-based chemotherapy in NSCLC patients, which may be prognostic biomarkers of chemotherapy if validated in larger studies.