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Topoisomerase 1 Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients.
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.
Afiliación
  • Paolicchi E; Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Oncology ; 91(5): 283-288, 2016.
Article en En | MEDLINE | ID: mdl-27577551
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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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Protocolos de Quimioterapia Combinada Antineoplásica / ADN-Topoisomerasas de Tipo I Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Oncology Año: 2016 Tipo del documento: Article País de afiliación: Italia
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Protocolos de Quimioterapia Combinada Antineoplásica / ADN-Topoisomerasas de Tipo I Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Oncology Año: 2016 Tipo del documento: Article País de afiliación: Italia