Seok-Hyun Kim1, Moon Jin Kim, Yu Ji Cho, Yi Yeong Jeong, Ho-Cheol Kim, Jong Duk Lee, Young Sil Hwang, In-Suk Kim, Suee Lee, Sung Yong Oh, Hui Ling, Gyeong-Won Lee. 1. *Department of Internal Medicine, Division of Hematology and Medical Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon †Department of Internal Medicine, Division of Hematology-Oncology, Gyeongsang National University School of Medicine ‡Department of Internal Medicine, Division of Pulmonology, Gyeongsang National University Hospital, Jinju §Department of Laboratory Medicine, Pusan National University School of Medicine, Busan ∥Department of Internal Medicine, Division of Hematology-Oncology, Dong-A University Medical Center, Busan, Republic of Korea ¶Department of Experimental Therapeutics, M.D. Anderson Cancer Center, University of Texas, Houston, TX.
Abstract
OBJECTIVES: The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mechanisms. Therefore, we investigated whether ABCG2 haplotype-tagging SNPs (htSNPs) were associated with clinical outcomes in patients with unresectable non-small cell lung cancer (NSCLC) treated with front-line platinum-based chemotherapy. PATIENTS AND METHODS: We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model. RESULTS: The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014). CONCLUSIONS: Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy.
OBJECTIVES: The ATP-binding cassette (ABC) ABCG2, involved in multidrug resistance (MDR) in cancer cells, plays an integral role in drug resistance. Single nucleotide polymorphisms (SNPs) have been identified in many MDR-associated ABC genes that seem to influence drug sensitivity/resistance through various mechanisms. Therefore, we investigated whether ABCG2 haplotype-tagging SNPs (htSNPs) were associated with clinical outcomes in patients with unresectable non-small cell lung cancer (NSCLC) treated with front-line platinum-based chemotherapy. PATIENTS AND METHODS: We genotyped 4 ABCG2 htSNPs for 129 unresectable NSCLC cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ABCG2 htSNP using the χ test, Kaplan-Meier method, and Cox proportional hazard model. RESULTS: The rs2725264 was significantly related to overall survival (OS) (P=0.018, log-rank test). The median survival duration (in months) for patients with the rs2725264 T/T, T/C, and C/C genotypes was 35.75 (95% confidence interval [CI], 24.25-47.25), 34.25 (hazard ratio [HR] 1.27 [0.68 to 2.35]; 95% CI, 27.16-41.34), and 14.89 (HR 3.22 [1.26 to 8.24], 95% CI, 13.86-15.92), respectively. The rs2725264 was identified as an independent factor by Cox proportional hazard model analysis (P=0.028). In the taxane-based groups, OS was associated with rs2725264 (P=0.041), whereas in the gemcitabine-based groups, OS was associated with rs4148149 (P=0.014). CONCLUSIONS: Our data suggest ABCG2 htSNPs rs2725264 (overall group and taxane-platinum combination group) and rs4148149 (gemcitabine-platinum combination group) were associated with OS in unresectable NSCLCpatients treated with first-line platinum-based chemotherapy. Thus, the ABCG2 htSNP rs2725264 may be independently associated with OS in unresectable NSCLCpatients treated with first-line platinum-based chemotherapy.
Authors: Anastasia Meshcheryakova; Martin Svoboda; Ammar Tahir; Harald C Köfeler; Alexander Triebl; Felicitas Mungenast; Georg Heinze; Christopher Gerner; Philip Zimmermann; Markus Jaritz; Diana Mechtcheriakova Journal: Oncotarget Date: 2016-04-19