Genome-wide association study of survival in non-small cell lung cancer patients receiving platinum-based chemotherapy

Xifeng Wu, Yuanqing Ye, Rafael Rosell, Christopher I. Amos, David J. Stewart, Michelle A.T. Hildebrandt, Jack A. Roth, John D. Minna, Jian Gu, Jie Lin, Shama C. Buch, Tomoko Nukui, Jose Luis Ramirez Serrano, Miquel Taron, Adrian Cassidy, Charles Lu, Joe Y. Chang, Scott M. Lippman, Waun Ki Hong, Margaret R. SpitzMarjorie Romkes, Ping Yang

Research output: Contribution to journalArticleResearchpeer-review

73 Citations (Scopus)

Abstract

Background Interindividual variation in genetic background may influence the response to chemotherapy and overall survival for patients with advanced-stage non-small cell lung cancer (NSCLC). Methods To identify genetic variants associated with poor overall survival in these patients, we conducted a genome-wide scan of 307 260 single-nucleotide polymorphisms (SNPs) in 327 advanced-stage NSCLC patients who received platinum-based chemotherapy with or without radiation at the University of Texas MD Anderson Cancer Center (the discovery population). A fast-track replication was performed for 315 patients from the Mayo Clinic followed by a second validation at the University of Pittsburgh in 420 patients enrolled in the Spanish Lung Cancer Group PLATAX clinical trial. A pooled analysis combining the Mayo Clinic and PLATAX populations or all three populations was also used to validate the results. We assessed the association of each SNP with overall survival by multivariable Cox proportional hazard regression analysis. All statistical tests were two-sided. Results SNP rs1878022 in the chemokine-like receptor 1 (CMKLR1) was statistically significantly associated with poor overall survival in the MD Anderson discovery population (hazard ratio [HR] of death = 1.59, 95% confidence interval [CI] = 1.32 to 1.92, P = 1.42 × 10-6), in the PLATAX clinical trial (HR of death = 1.23, 95% CI = 1.00 to 1.51, P =. 05), in the pooled Mayo Clinic and PLATAX validation (HR of death = 1.22, 95% CI = 1.06 to 1.40, P =. 005), and in pooled analysis of all three populations (HR of death = 1.33, 95% CI = 1.19 to 1.48, P = 5.13 × 10-7). Carrying a variant genotype of rs10937823 was associated with decreased overall survival (HR of death = 1.82, 95% CI = 1.42 to 2.33, P = 1.73 × 10-6) in the pooled MD Anderson and Mayo Clinic populations but not in the PLATAX trial patient population (HR of death = 0.96, 95% CI = 0.69 to 1.35). Conclusion These results have the potential to contribute to the future development of personalized chemotherapy treatments for individual NSCLC patients. © The Author 2011. Published by Oxford University Press. All rights reserved.
Original languageEnglish
Pages (from-to)817-825
JournalJournal of the National Cancer Institute
Volume103
Issue number10
DOIs
Publication statusPublished - 18 May 2011

Fingerprint Dive into the research topics of 'Genome-wide association study of survival in non-small cell lung cancer patients receiving platinum-based chemotherapy'. Together they form a unique fingerprint.

  • Cite this

    Wu, X., Ye, Y., Rosell, R., Amos, C. I., Stewart, D. J., Hildebrandt, M. A. T., Roth, J. A., Minna, J. D., Gu, J., Lin, J., Buch, S. C., Nukui, T., Ramirez Serrano, J. L., Taron, M., Cassidy, A., Lu, C., Chang, J. Y., Lippman, S. M., Hong, W. K., ... Yang, P. (2011). Genome-wide association study of survival in non-small cell lung cancer patients receiving platinum-based chemotherapy. Journal of the National Cancer Institute, 103(10), 817-825. https://doi.org/10.1093/jnci/djr075