Inflammation-related Genetic Variations and Survival for Advanced Non-Small Cell Lung Cancer Receiving First-line Chemotherapy

BACKGROUND: accurate prognostic prediction is challenging for advanced-stage non-small cell lung cancer (NSCLC) patients. METHODS: we systematically investigated genetic variants within inflammation pathway as potential prognostic markers for advanced-stage NSCLC patients treated with first-line chemotherapy. A discovery phase in 502 patients and an internal validation in 335 patients were completed at MD Anderson Cancer Center. External validation was performed in 371 patients at Harvard University. RESULTS: a missense SNP (HLA-DOB:rs2071554) predicted to influence protein function was significantly associated with poor survival in the discovery (HR:1.46, 95% CI:1.02-2.09), internal validation (HR:1.51, 95% CI:1.02-2.25), and external validation (HR:1.52, 95% CI:1.01-2.29) populations. KLRK1:rs2900420 was associated with a reduced risk in the discovery (HR:0.76, 95% CI:0.60-0.96), internal validation (HR:0.77, 95% CI:0.61-0.99), and external validation (HR:0.80, 95% CI:0.63-1.02) populations. A strong cumulative effect was observed for these SNPs on overall survival. CONCLUSIONS: Genetic variations in inflammation-related genes could have potential to complement prediction of prognosis.