title: Predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype in small cell lung cancer patients treated with chemotherapy.
abstract: OBJECTIVE
  Multiple drug resistance limits the efficacy of numerous cytotoxic drugs used in the treatment of small cell lung cancer (SCLC). The drug efflux protein ATP-binding cassette transporter B1 (ABCB1) has an important role in this process, and its gene variability may affect chemotherapy outcomes.
  
  
  METHODS
  This study aimed to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in 177 SCLC patients treated with cisplatin-etoposide or cyclophosphamide-epirubicin-vincristine chemotherapy. To determine the ABCB1 genotype, allelic specific TaqMan(®) probes were used in a RT-PCR .
  
  
  RESULTS
  Patients carrying the G2677T/A TT + TA + AA genotypes (24 %) or the C3435T CT + TT genotypes (72 %) or the 2677T/A-3435T haplotype (40 %) had a longer PFS (Cox regression, P = 0.052, 0.037 and 0.037, respectively); these associations persisted also in multivariate analyses (Cox regression, P = 0.028, 0.037 and 0.030, respectively). Moreover, patients with the C3435T CT + TT genotypes had a longer OS both in univariate and multivariate analysis (Cox regression, P = 0.022 and 0.028, respectively). A trend toward longer OS was noted for the 2677T/A-3435T haplotype (Cox regression, P = 0.051), but its independent value was not confirmed (Cox regression, P = 0.071).
  
  
  CONCLUSIONS
  Our study reported a possible predictive value of ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype for longer PFS and OS in Caucasian SCLC patients treated with chemotherapy. However, to be implemented into routine clinical practice, ABCB1 polymorphisms require further validation.
authors.affiliation: University Hospital Golnik, Golnik 36, 4204, Golnik, Slovenia. lea.knez@klinika-golnik.si
authors.forename: L
authors.initials: L
authors.lastname: Knez
authors.forename: M
authors.initials: M
authors.lastname: Košnik
authors.forename: T
authors.initials: T
authors.lastname: Ovčariček
authors.forename: A
authors.initials: A
authors.lastname: Sadikov
authors.forename: E
authors.initials: E
authors.lastname: Sodja
authors.forename: I
authors.initials: I
authors.lastname: Kern
authors.forename: T
authors.initials: T
authors.lastname: Cufer
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015251:Epirubicin; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin