Kyong-Ah Yoon 1 , Mee Kyung Jung 1 , Donghoon Lee 1 , Kieun Bae 1 , Jung Nam Joo 1 , Geon Kook Lee 1 , Hyun-Sung Lee 2 , Jin Soo Lee 2 Show Affiliations »
Abstract
PURPOSE: Postoperative recurrence in stage I non-small cell lung cancer (NSCLC) is the major cause of a poor prognosis. This study aims to identify genetic variants that are associated with the prognosis of early-stage NSCLCs. EXPERIMENTAL DESIGN: A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLCs and the results were replicated in additional 308 patients. RESULTS: Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 SNPs with significant associations (P < 2 × 10(-4)), which were selected for replication in 308 additional patients. Pooled analysis of the 558 patients determined that rs1454694 in chromosome 4q34 was the most significant marker of lung cancer prognosis in the stage I patients (adjusted HR = 2.81; P = 5.91 × 10(-8)). After the candidate loci were mapped, an additional four markers at chromosome 4q34.3 were significantly associated with recurrence-free survival (RFS; P < 5 × 10(-5)). A haplotype of five SNPs in 4q34 also showed significant association with RFS (P = 4.29 × 10(-6)). CONCLUSIONS: A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs. ©2014 American Association for Cancer Research.
PURPOSE: Postoperative recurrence in stage I non-small cell lung cancer (NSCLC ) is the major cause of a poor prognosis. This study aims to identify genetic variants that are associated with the prognosis of early-stage NSCLCs. EXPERIMENTAL DESIGN: A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLCs and the results were replicated in additional 308 patients . RESULTS: Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 SNPs with significant associations (P < 2 × 10(-4)), which were selected for replication in 308 additional patients . Pooled analysis of the 558 patients determined that rs1454694 in chromosome 4q34 was the most significant marker of lung cancer prognosis in the stage I patients (adjusted HR = 2.81; P = 5.91 × 10(-8)). After the candidate loci were mapped, an additional four markers at chromosome 4q34.3 were significantly associated with recurrence-free survival (RFS; P < 5 × 10(-5)). A haplotype of five SNPs in 4q34 also showed significant association with RFS (P = 4.29 × 10(-6)). CONCLUSIONS: A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for RFS of stage I NSCLCs. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs. ©2014 American Association for Cancer Research.
Entities: Disease
Gene
Mutation
Species
Mesh： See more »
Substances： See more »
Year: 2014
PMID： 24737549 DOI： 10.1158/1078-0432.CCR-13-2835
Source DB: PubMed Journal: Clin Cancer Res ISSN： 1078-0432 Impact factor: 12.531