Abstract
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. 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 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)). 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.
Highlights
Lung cancer is the leading cause of cancer mortality worldwide [1,2,3]
A genetic polymorphism rs1454694 was identified as a novel genetic risk factor for recurrence-free survival (RFS) of stage I non–small cell lung cancer (NSCLC)
This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLCs
Summary
Lung cancer is the leading cause of cancer mortality worldwide [1,2,3]. In Korea, non–small cell lung cancer (NSCLC) constitutes the majority of all diagnosed lung cancers with 70% of patients with NSCLCs being diagnosed at stages III and IV and only 17% at stage I [4, 5]. The overall survival (OS) of patients with advanced NSCLCs remains poor, whereas the survival time in early-stage patients has improved. Of those patients in pathologic stage IA and IB NSCLCs who are candidates for surgical resection, the 5-year OS rates are approximately 73% and 58%, respectively [6, 7]. While postoperative adjuvant chemotherapy is the standard care among patients with stage II to IIIA NSCLCs who have undergone complete resections, surgery remains the only recommended guideline for the treatment of stage I NSCLCs. The recurrence rate in stage I patients who underwent surgical resection ranges from 13% to 41% [8, 9]
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