title: Topoisomerase 1 Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients.
abstract: OBJECTIVE
  Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients.
  
  
  METHODS
  With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival).
  
  
  RESULTS
  No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1).
  
  
  CONCLUSIONS
  Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens.
authors: Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors: Elisa
authors: E
authors: Paolicchi
authors: Caterina
authors: C
authors: Vivaldi
authors: Veronica
authors: V
authors: De Gregorio
authors: Francesco
authors: F
authors: Crea
authors: Lorenzo
authors: L
authors: Fornaro
authors: Gianluca
authors: G
authors: Masi
authors: Fotios
authors: F
authors: Loupakis
authors: Francesco
authors: F
authors: Graziano
authors: Monica
authors: M
authors: Ronzoni
authors: Vincenzo
authors: V
authors: Ricci
authors: Alfredo
authors: A
authors: Falcone
authors: Romano
authors: R
authors: Danesi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004264:DNA Topoisomerases, Type I / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D066066:Response Evaluation Criteria in Solid Tumors; D015996:Survival Rate
chemical_list: D000068258:Bevacizumab; D000077146:Irinotecan; D004264:DNA Topoisomerases, Type I; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin