Genome-wide association study on overall survival of advanced non-small cell lung cancer patients treated with carboplatin and paclitaxel

Yasunori Sato, Noboru Yamamoto, Hideo Kunitoh, Yuichiro Ohe, Hironobu Minami, Nan M. Laird, Noriko Katori, Yoshiro Saito, Sumiko Ohnami, Hiromi Sakamoto, Jun Ichi Sawada, Nagahiro Saijo, Teruhiko Yoshida, Tomohide Tamura

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36 Citations (Scopus)

Abstract

PURPOSE: Our goal was to identify candidate polymorphisms that could influence overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated with carboplatin (CBDCA) and paclitaxel (PTX). METHODS: Chemotherapy-naïve stage IIIB or IV NSCLC patients treated with CBDCA (area under the curve = 6 mg/mL/min) and PTX (200 mg/m2, 3-hour period) were eligible for this study. The DNA samples were extracted from peripheral blood mononuclear cells before treatment, and genotypes at approximately 110,000 gene-centric single-nucleotide polymorphisms (SNPs) were obtained by Illumina's Sentrix Human-1 Genotyping BeadChip. Statistical analyses were performed by the log-rank test and Cox proportional hazards model. RESULTS: From July 2002 to May 2004, 105 patients received a total of 308 cycles of treatment. The median survival time (MST) of 105 patients was 17.1 months. In the genome-wide association study, three SNPs were associated significantly with shortened OS after multiple comparison adjustment: rs1656402 in the EIF4E2 gene (MST was 18.0 and 7.7 months for AG [n = 50] + AA [n = 40] and GG [n = 15], respectively; p = 8.4 × 10-8), rs1209950 in the ETS2 gene (MST = 17.7 and 7.4 months for CC [n = 94] and CT [n = 11] + TT [n = 0]; p = 2.8 × 10 -7), and rs9981861 in the DSCAM gene (MST = 17.1 and 3.8 months for AA [n = 75] + AG [n = 26] and GG [n = 4]; p = 3.5 × 10-6). CONCLUSION: Three SNPs were identified as new prognostic biomarker candidates for advanced NSCLC treated with CBDCA and PTX. The agnostic genome-wide association study may unveil unexplored molecular pathways associated with the drug response, but our findings should be replicated by other investigators.

Original languageEnglish
Pages (from-to)132-138
Number of pages7
JournalJournal of Thoracic Oncology
Volume6
Issue number1
DOIs
Publication statusPublished - 2011 Jan
Externally publishedYes

Keywords

  • Advanced non-small lung cancer
  • Carboplatin
  • Genome-wide association study
  • Paclitaxel
  • Single-nucleotide polymorphisms

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Sato, Y., Yamamoto, N., Kunitoh, H., Ohe, Y., Minami, H., Laird, N. M., Katori, N., Saito, Y., Ohnami, S., Sakamoto, H., Sawada, J. I., Saijo, N., Yoshida, T., & Tamura, T. (2011). Genome-wide association study on overall survival of advanced non-small cell lung cancer patients treated with carboplatin and paclitaxel. Journal of Thoracic Oncology, 6(1), 132-138. https://doi.org/10.1097/JTO.0b013e318200f415