A genome-wide association study of survival in small-cell lung cancer patients treated with irinotecan plus cisplatin chemotherapy

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Title
A genome-wide association study of survival in small-cell lung cancer patients treated with irinotecan plus cisplatin chemotherapy
Author(s)
J Y Han; Y S Lee; E S Shin; J A Hwang; S Nam; S H Hong; Hoyoung Ghang; J Y Kim; S J Yoon; J S Lee
Bibliographic Citation
Pharmacogenomics Journal, vol. 14, no. 1, pp. 20-27
Publication Year
2014
Abstract
We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) influencing overall survival (OS) of small-cell lung cancer (SCLC) patients. We prospectively collected blood samples from 139 SCLC patients who participated in phase II studies of irinotecan and cisplatin (IP) chemotherapy as first-line therapy. Among 334 127 SNPs, which passed quality control, seven showed significant association with OS. The rs16950650CT, rs7186128AG or GG, rs17574269AG, rs8020368CC, rs4655567CC, rs2166219TT or rs2018683TT showed shorter OS compared with control alleles. Among the seven SNPs, rs4655567, rs8020368 and rs2018683 were significantly associated with a resistant relapse (RR). In the multivariate analysis, rs8020368CC was significantly associated with higher risk of RR (odds ratio=16.7, P=0.007). In vitro and in silico analysis showed that SNPs in C14orf49 might be associated with epithelial-to-mesenchymal transition. This exploratory GWAS identified candidate SNPs that may be predictive of the clinical outcome of SCLC patients receiving IP.
Keyword
C14orf49GWASSCLCsurvival
ISSN
1470-269X
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/tpj.2013.7
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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