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- Title
Topoisomerase 1 Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients.
- Authors
Paolicchi, Elisa; Vivaldi, Caterina; De Gregorio, Veronica; Crea, Francesco; Fornaro, Lorenzo; Masi, Gianluca; Loupakis, Fotios; Graziano, Francesco; Ronzoni, Monica; Ricci, Vincenzo; Falcone, alfredo; Danesi, Romano
- 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.
- Subjects
ENZYMES; DNA analysis; CARRIER proteins; COLON tumors; CONFIDENCE intervals; GENETIC polymorphisms; METASTASIS; POLYMERASE chain reaction; DESCRIPTIVE statistics; RECTUM tumors; IRINOTECAN; GENOTYPES; PHYSIOLOGY; GENETICS
- Publication
Oncology, 2016, Vol 91, Issue 5, p283
- ISSN
0030-2414
- Publication type
Article
- DOI
10.1159/000448004