A genome-wide association study for irinotecan-related severe toxicities in patients with advanced non-small-cell lung cancer

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Title
A genome-wide association study for irinotecan-related severe toxicities in patients with advanced non-small-cell lung cancer
Author(s)
J Y Han; E S Shin; Y S Lee; Hoyoung Ghang; S Y Kim; J A Hwang; J Y Kim; J S Lee
Bibliographic Citation
Pharmacogenomics Journal, vol. 13, no. 5, pp. 417-422
Publication Year
2013
Abstract
The identification of patients who are at high risk for irinotecan-related severe diarrhea and neutropenia is clinically important. We conducted the first genome-wide association study (GWAS) to search for novel susceptibility genes for irinotecan-related severe toxicities, such as diarrhea and neutropenia, in non-small-cell lung cancer (NSCLC) patients treated with irinotecan chemotherapy. The GWAS putatively identified 49 single-nucleotide polymorphisms (SNPs) associated with grade 3 diarrhea (G3D) and 32 SNPs associated with grade 4 neutropenia (G4N). In the replication series, the SNPs rs1517114 (C8orf34), rs1661167 (FLJ41856) and rs2745761 (PLCB1) were confirmed as being associated with G3D, whereas rs11128347 (PDZRN3) and rs11979430 and rs7779029 (SEMAC3) were confirmed as being associated with G4N. The final imputation analysis of our GWAS and replication study showed significant overlaps of association signals within these novel variants. This GWAS screen, along with subsequent validation and imputation analysis, identified novel SNPs associated with irinotecan-related severe toxicities.
Keyword
C8orf34FLJ41856irinotecanPDZRN3PLCB1SEMA3C
ISSN
1470-269X
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/tpj.2012.24
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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