The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma

• DOI: 10.1097/fpc.0b013e32834e3572
• Publication Date: 2011-12-01T17:53:57Z
• Authors: Nina Erčulj; Viljem Kovač; Julija Hmeljak; Alenka Franko; Metoda Dodič-Fikfak; Vita Dolžan
• Keywords: GSTP1

Identification of biomarkers that could predict gemcitabine efficacy and toxicity is a key issue in the development individualized therapy. The aim our study was to evaluate influence pathway polymorphisms on treatment outcome patients with malignant mesothelioma (MM).In total, 107 MM, treated gemcitabine-platinum chemotherapy, were genotyped for 11 deoxycytidine kinase, ribonucleotide reductase M1 (RRM1), cytidine deaminase genes using KASPar assays. Binary logistic regression used selected tumor response occurrence treatment-related toxicity, while their survival estimated by Cox proportional hazards model. A haplotype analysis carried out assess combined effect RRM1 polymorphisms.Deoxycytidine kinase did not MM. In multivariable analysis, 2927A>C polymorphism significantly decreased overall probability [hazard ratio (HR)=2.02; 95% confidence interval (CI)=1.11-3.65; P=0.021]. Two promoter polymorphisms, -524T>C -37C>A, odds nausea/vomiting grade≥2 [odds (OR)=0.25; CI=0.10-0.60; P=0.002 OR=0.26; CI=0.11-0.63; P=0.003, respectively]. TTCCA associated worse (OR=16.67; CI=2.38-100.00; P=0.004) (HR=2.97; CI=1.46-6.06; P=0.003) compared most frequent TTCAA haplotype, TCACA influenced (OR=0.27; CI=0.12-0.60; P=0.001).RRM1 as well haplotypes showed an association toxicity; therefore, they should be validated potential markers prediction clinical