Genome-wide association study of myelosuppression in non-small-cell lung cancer patients with platinum-based chemotherapy.

Platinum-induced myelosuppression severely impedes successful chemotherapy in non-small-cell lung cancer (NSCLC) patients. Hence, it is clinically important to identify the patients who are at high risk for severe toxicity to certain chemotherapy. We first carried out a genome-wide scan of 906 703 single-nucleotide polymorphisms (SNPs) to identify genetic variants associated with platinum-induced myelosuppression risk in 333 NSCLC patients with chemotherapy. Then, we replicated 24 SNPs that had P<1 × 10(-4) in another independent cohort of 876 NSCLC patients. With P<0.05 as the criterion of statistical significance, we found that rs13014982 at 2q24.3 and rs9909179 at 17p12 exhibited consistently significant associations with myelosuppression risk in both the genome-wide association studies (GWAS) scan and the replication stage (rs13014982: odds ratio (OR)=0.55, 95% confidence intervals (CIs): 0.41-0.74, P=7.29 × 10(-5) for GWAS scan and OR=0.77, 95% CI: 0.65-0.93, P=0.006 for replication stage; rs9909179: OR=0.51, 95% CI: 0.37-0.70, P=4.60 × 10(-5) for GWAS scan and OR=0.82, 95% CI: 0.68-0.99, P=0.040 for replication stage; both in additive model). In combined samples of genome-wide scan and replication samples, the minor alleles of rs13014982 and rs9909179 remained significant associations with the decreased risk of myelosuppression (rs13014982: OR=0.71, 95% CI: 0.61-0.83, P =1.36 × 10(-5); rs9909179: OR=0.76, 95% CI: 0.65-0.89, P=0.001). Rs13014982 at 2q24.3 and rs9909179 at 17p12 might be independent susceptibility markers for platinum-induced myelosuppression risk in NSCLC patients.