Genome-wide association study of survival in early-stage non-small cell lung cancer

Abstract

Background: Lung cancer, especially non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths all over the world. Studies have indicated that molecular biomarkers, including genetic variants, may provide additional values for the targeted treatments and clinical outcomes of NSCLC patients. To better understand the effects of molecular biomarkers on the treatment of NSCLC, we conducted a genome-wide analysis to investigate the prognostic implications of genetic variants in early-stage NSCLC patients with surgery.

Methods: A genome wide scan of 906,703 single-nucleotide polymorphisms (SNPs) was conducted in a cohort with 365 early-stage NSCLC patients with surgery, followed by a fast-track replication in another independent cohort of 327 NSCLC patients from Nanjing, China. Cox models were used to screen and validate significant SNPs associated with the overall survival of early-stage NSCLC patients.

Results: We found that rs10023113 in calcium/calmodulin-dependent protein kinase II delta (CAMK2D) was consistently associated with survival of early-stage NSCLC in the GWAS scan and the replication cohort [GWAS scan: hazard ratio (HR) 2.84; 95 % confidence interval (CI) 1.90-4.23, P = 1.29 × 10(-6); replication cohort: HR 2.19, 95 % CI 1.15-4.21, P = 1.80 × 10(-2)]. When combining all the patients, the results showed that the variant allele of rs10023113 was significantly associated with poor prognosis of early-stage NSCLC with P value of 3.40 × 10(-7) (HR 2.30, 95 % CI 1.67-3.17).

Conclusions: These findings suggest that CAMK2D rs10023113 may be a potentially prognostic marker for overall survival of early-stage NSCLC patients in Chinese population.