Topoisomerase 1 Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Elisa Paolicchi, Caterina Vivaldi, Veronica De Gregorio, Francesco Crea, Lorenzo Fornaro, Gianluca Masi, Fotios Loupakis, Francesco Graziano, Monica Ronzoni, Vincenzo Ricci, Alfredo Falcone, Romano Danesi

Research output: Contribution to journalArticlepeer-review

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). Conclusion: 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.

Original languageEnglish
JournalOncology
DOIs
Publication statusAccepted/In press - Aug 31 2016
Externally publishedYes

Keywords

  • <italic>Topoisomerase 1</italic>
  • FOLFIRI
  • Metastatic colorectal cancer
  • Single-nucleotide polymorphism
  • Transcription factor binding

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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