Genetic variations associated with postoperative recurrence in stage I non-small-cell lung cancer
Menée sur 250 patients atteints d'un cancer du poumon non à petites cellules de stade I puis sur 308 autres patients, cette étude coréenne identifie des variants génétiques associés à la survie sans récidive des patients
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 associated with the prognosis of early stage NSCLC.
Experimental Design : A genome-wide association study (GWAS) was conducted in 250 patients in stage I NSCLC and the results were replicated in additional 308 patients.
Results : Results from an Affymetrix Genome-wide Human SNP array in 250 patients identified 94 single nucleotide polymorphisms (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 this stage I patients (adjusted hazard ratio (HR) = 2.81; p = 5.91×10-8). After mapping the candidate loci, 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 recurrence free survival of stage I NSCLC. This genome-wide study suggests that genetic markers in 4q34.3 contribute to predict the prognosis of Korean patients with stage I NSCLC.
Clinical Cancer Research , résumé, 2014