title: A genome-wide association study of survival in small-cell lung cancer patients treated with irinotecan plus cisplatin chemotherapy.
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.
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Han
authors.affiliation: Functional Genomic Branch, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: Y-S
authors.initials: YS
authors.lastname: Lee
authors.affiliation: DNALink, Seoul, Republic of Korea.
authors.forename: E Soon
authors.initials: ES
authors.lastname: Shin
authors.affiliation: Functional Genomic Branch, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: J-A
authors.initials: JA
authors.lastname: Hwang
authors.affiliation: Functional Genomic Branch, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Nam
authors.affiliation: Functional Genomic Branch, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: H Young
authors.initials: HY
authors.lastname: Ghang
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: J Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: S Jin
authors.initials: SJ
authors.lastname: Yoon
authors.affiliation: Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea.
authors.forename: J Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D003627:Data Interpretation, Statistical; D018572:Disease-Free Survival; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin