title: Clinical Significance of ABCG2 Haplotype-tagging Single Nucleotide Polymorphisms in Patients With Unresectable Non-Small Cell Lung Cancer Treated With First-line Platinum-based Chemotherapy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: *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.
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Moon Jin
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yu Ji
authors.initials: YJ
authors.lastname: Cho
authors.forename: Yi Yeong
authors.initials: YY
authors.lastname: Jeong
authors.forename: Ho-Cheol
authors.initials: HC
authors.lastname: Kim
authors.forename: Jong Duk
authors.initials: JD
authors.lastname: Lee
authors.forename: Young Sil
authors.initials: YS
authors.lastname: Hwang
authors.forename: In-Suk
authors.initials: IS
authors.lastname: Kim
authors.forename: Suee
authors.initials: S
authors.lastname: Lee
authors.forename: Sung Yong
authors.initials: SY
authors.lastname: Oh
authors.forename: Hui
authors.initials: H
authors.lastname: Ling
authors.forename: Gyeong-Won
authors.initials: GW
authors.lastname: Lee
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D001952:Bridged-Ring Compounds; D009363:Neoplasm Proteins; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine