Genome-wide association study of myelosuppression in non-small-cell lung cancer patients with platinum-based chemotherapy
Genome-wide association study of myelosuppression in non-small-cell lung cancer patients with platinum-based chemotherapy
复制标题
铂类化疗非小细胞肺癌患者骨髓抑制的全基因组关联研究
DOI：
10.1038/tpj.2015.22
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发表时间：
2016-02-01
影响因子：
2.8
通讯作者：
Shen, H.
中科院分区：
文献类型：
--
作者：
Cao, S.;Wang, S.;Shen, H.
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.
