Genetic variants in cytokine signaling pathways and clinical outcomes in early-stage lung cancer patients

Objectives: The purpose of this study was to explore the role of single nucleotide polymorphisms (SNPs) in cytokine signaling genes and to compare them with clinical outcomes in surgical patients with non-small cell lung cancer (NSCLC).

Methods: SNPs of the cytokine signaling pathway were analyzed using peripheral blood of 722 patients who underwent resection of stage I to III NSCLC between 1995 and 2009. Cox proportional hazard analyses were performed to identify SNPs associated with overall survival (OS) and risk of recurrence. Internal validation using bootstrap analysis selected SNPs for unfavorable genotype and survival tree analysis.

Results: Seventeen and 9 SNPs were independently associated with OS and recurrence, respectively. Patients with ≥9 unfavorable genotypes experienced worse OS (median, 41 months) than patients with 7 to 8 (89 months) and ≤6 (153 months) after median follow-up of 71 months (P = 2.86 × 10^-23). Patients with ≤3 unfavorable genotypes had greater time to recurrence (median not reached) than those with 4 to 6 (114 months) and ≥7 (44 months; P = 1.3 × 10^-5). Survival tree analysis classified patients into 3 risk groups. Patients in the intermediate- (median OS, 82 months) and high-risk groups (43 months) had worse survival than the low-risk group (176 months; P = 5.51 × 10^-20). Median time to recurrence was worse in the intermediate- (114 months) and high-risk groups (58 months) than the low-risk group (median not reached; P = 2.52 × 10^-9).

Conclusions: Genetic variants in cytokine signaling pathways were associated with clinical outcomes in NSCLC patients treated with surgery individually and cumulatively. Further studies are necessary to elucidate our findings and translate them into the clinical setting.