GWAS study of myelosuppression among NSCLC patients receiving platinum-based combination chemotherapy

Platinum-based chemotherapy remains the mainstay for non-small cell lung cancer (NSCLC), but it frequently causes dose-limiting myelosuppression, with significant individual variability in susceptibility. However, the genetic basis of myelosuppression side effects remains elusive, greatly hindering personalized therapeutic approaches. In this study, we perform a comprehensive genome-wide association analysis on 491 NSCLC patients receiving platinum-based chemotherapy, examining 4,690,998 single-nucleotide polymorphisms (SNPs) to identify relevant genetic variants. LDBlockShow, FUMA, and MAGMA are utilized to explore linkage disequilibrium, expression quantitative trait loci (eQTLs), chromatin interaction, and conduct gene-based and gene set-based analysis of candidate SNPs. The GWAS results reveal that rs6856089 and its linked SNPs are significantly associated with platinum-based chemotherapy-induced myelosuppression. Specifically, patients with the A allele of rs6856089 have a significantly lower risk of myelosuppression [odds ratio (OR) = 0.1300, P  = 7.59 × 10 ^-8]. Furthermore, gene-based analysis reveals that EMCN ( P  = 2.47 × 10 ^-5), which encodes endomucin, a marker for hematopoietic stem cells, might mediate myelosuppression. This study provides a scientific basis for the individual differences in platinum-based chemotherapy-induced myelosuppression.