A two-stage genome-wide association study to identify germline polymorphisms associated with survival of...

The effect of genetic polymorphisms on survival outcomes in nasopharyngeal carcinoma (NPC) has not been fully elucidated. This study aimed to identify genetic variants associated with NPC survival using a genome-wide association study (GWAS) approach.

We performed a two-stage GWAS involving a total of 783 NPC patients. In the discovery phase, 303 individuals were genotyped for 688,783 single-nucleotide polymorphisms (SNPs) using the whole-genome screening microarray. The Cox proportional hazards regression model was applied to screen for SNPs associated with overall survival (OS) or progression-free survival (PFS). The candidate SNPs were subsequently validated in an independent cohort of 480 patients using the MassARRAY system. Bioinformatic analyses were conducted using bioinformatics software and databases including LocusZoom, LDBlockShow, eQTLGen, and RegulomeDB. Finally, we integrated the genetic variant and clinical factors to develop survival prediction models for NPC.

Our results demonstrated that rs17771861 on chromosome 6p22.3 was significantly associated with OS and PFS in NPC patients following validation. Subgroup analyses further indicated that rs17771861 was correlated with poor OS and PFS in male patients, those with advanced-stage disease (Stage III + IV), and patients who received concurrent chemoradiotherapy. Additionally, survival prediction models integrating the genetic variant and clinical factors were constructed for OS and PFS, and these models exhibited superior predictive performance compared to models based only on clinical factors.

Our study identified that rs17771861 was associated with OS and PFS in patients with NPC, suggesting that this locus may serve as a novel genetic biomarker for survival stratification in NPC.