title: Inflammation-related genetic variations and survival in patients with advanced non-small cell lung cancer receiving first-line chemotherapy.
abstract: Accurate prognostic prediction is challenging for patients with advanced-stage non-small cell lung cancer (NSCLC). We systematically investigated genetic variants within inflammation pathways as potential prognostic markers for advanced-stage NSCLC patients treated with first-line chemotherapy. A discovery phase in 502 patients and an internal validation phase in 335 patients were completed at the MD Anderson Cancer Center. External validation was performed in 371 patients at Harvard University. A missense single-nucleotide polymorphism (SNP) in the gene encoding the major histocompatibility complex class II, DO-β chain (HLA-DOB:rs2071554), predicted to influence protein function, was significantly associated with poor survival in the discovery (hazard ratio (HR): 1.46; 95% confidence interval (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 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 on overall survival was observed for these SNPs. Genetic variations in inflammation-related genes could have potential to complement prediction of prognosis.
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Pu
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hildebrandt
authors.affiliation: Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.affiliation: Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.affiliation: Division of Medical Oncology, The Ottawa Hospital Cancer Center, Ottawa, Ontario.
authors.forename: David J
authors.initials: DJ
authors.lastname: Stewart
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heist
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Chang
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.affiliation: Rebecca and John Moores Cancer Center, The University of California San Diego, San Diego, CA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.affiliation: The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.affiliation: Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001900:Boston; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D059248:Chemoradiotherapy; D005260:Female; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics*; D009367:Neoplasm Staging; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012307:Risk Factors; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006681:HLA-D Antigens; C046148:HLA-DO antigens; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K
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