Clinical Pharmacology & Therapeutics - Abstract of article: Inflammation-Related Genetic Variations and Survival in Patients With Advanced Non-Small Cell Lung Cancer Receiving First-Line Chemotherapy

Clinical Pharmacology & Therapeutics - Abstract of article: Inflammation-Related Genetic Variations and Survival in Patients With Advanced Non-Small Cell Lung Cancer Receiving First-Line Chemotherapy

Articles

Clinical Pharmacology & Therapeutics advance online publication 4 June 2014; doi: 10.1038/clpt.2014.89

Inflammation-Related Genetic Variations and Survival in Patients With Advanced Non–Small Cell Lung Cancer Receiving First-Line Chemotherapy

X Pu¹, M A T Hildebrandt¹, C Lu², J A Roth³, D J Stewart⁴, Y Zhao⁵, R S Heist⁶, Y Ye¹, D W Chang¹, L Su⁵, J D Minna⁷, S M Lippman⁸, M R Spitz⁹, D C Christiani^5,6and X Wu¹

1. ¹Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
2. ²Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3. ³Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
4. ⁴Division of Medical Oncology, The Ottawa Hospital Cancer Center, Ottawa, Ontario, Canada
5. ⁵Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
6. ⁶Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
7. ⁷Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
8. ⁸Rebecca and John Moores Cancer Center, The University of California, San Diego, San Diego, California, USA
9. ⁹The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA

Correspondence: X Wu, (xwu@mdanderson.org)

The first two authors contributed equally to this work; the last three authors contributed equally to this work.

Received 24 February 2014; Accepted 15 April 2014
Accepted article preview online 22 April 2014; Advance online publication 4 June 2014

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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.