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/m, 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), 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), 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). 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.
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 NSCLCpatients treated with CBDCA (area under the curve = 6 mg/mL/min) and PTX (200 mg/m, 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), 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), 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). 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.
Authors: Carissa C Jones; William S Bush; Dana C Crawford; Angela S Wenzlaff; Ann G Schwartz; John K Wiencke; Margaret R Wrensch; William J Blot; Stephen J Chanock; Eric L Grogan; Melinda C Aldrich Journal: Cancer Epidemiol Biomarkers Prev Date: 2017-06-15 Impact factor: 4.254
Authors: Joel L Weissfeld; Brenda Diergaarde; Tomoko Nukui; Shama Buch; Arjun Pennathur; Mark A Socinski; Jill M Siegfried; Marjorie Romkes Journal: J Thorac Oncol Date: 2014-09 Impact factor: 15.609
Authors: Xifeng Wu; Liang Wang; Yuanqing Ye; Jeremiah A Aakre; Xia Pu; Gee-Chen Chang; Pan-Chyr Yang; Jack A Roth; Randolph S Marks; Scott M Lippman; Joe Y Chang; Charles Lu; Claude Deschamps; Wu-Chou Su; Wen-Chang Wang; Ming-Shyan Huang; David W Chang; Yan Li; V Shane Pankratz; John D Minna; Waun Ki Hong; Michelle A T Hildebrandt; Chao Agnes Hsiung; Ping Yang Journal: Cancer Res Date: 2013-05-23 Impact factor: 12.701
Authors: Xia Pu; Jack A Roth; Michelle A T Hildebrandt; Yuanqing Ye; Hua Wei; John D Minna; Scott M Lippman; Xifeng Wu Journal: Cancer Res Date: 2013-02-01 Impact factor: 12.701