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

Paolicchi, E.; Vivaldi, C.; De Gregorio, V.; Crea, F.; Fornaro, L.; Masi, G.; Loupakis, F.; Graziano, F.; Ronzoni, M.; Ricci, V.; Falcone, A. and Danesi, R. (2016). Topoisomerase 1 Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients. Oncology, 91(5) pp. 283–288.

DOI: https://doi.org/10.1159/000448004

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.

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