The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC PatientsReport as inadecuate




The Effectiveness of Pemetrexed Monotherapy Depending on Polymorphisms in TS and MTHFR Genes as Well as Clinical Factors in Advanced NSCLC Patients - Download this document for free, or read online. Document in PDF available to download.

Pathology and Oncology Research

, Volume 22, Issue 1, pp 49–56

First Online: 16 August 2015Received: 20 November 2014Accepted: 03 August 2015DOI: 10.1007-s12253-015-9966-z

Cite this article as: Kucharczyk, T., Krawczyk, P., Powrózek, T. et al. Pathol. Oncol. Res. 2016 22: 49. doi:10.1007-s12253-015-9966-z

Abstract

In NSCLC, second-line chemotherapy using pemetrexed or docetaxel has limited efficacy and should be dedicated to selected groups of patients. Pemetrexed is an antifolate compound with the ability to inhibit enzymes TS, DHFR and GARFT involved in pyrimidine and purine synthesis. The objective of this study was to evaluate the association between polymorphisms of TS and MHFR genes and clinical outcomes in NSCLC patients treated with pemetrexed monotherapy. DNA was isolated from peripheral blood of 72 non-squamous NSCLC patients treated with pemetrexed. Using PCR and RFLP methods, the variable number of tandem repeats VNTR, the G > C SNP in these repeats and insertion-deletion polymorphism of TS gene as well as 677C > T SNP in MTHFR gene were analyzed and correlated with disease control rate, progression-free survival and overall survival OS of NSCLC patients. Carriers of 2R-3RG, 3RC-3RG, 3RG-3RG genotypes showed significantly more frequent early progression than carriers of 2R-2R, 2R-3RC, 3RC-3RC genotypes of TS gene p < 0.05. Among carriers of triple 28 bp tandem repeats 3R in TS gene and C-C genotype of MTHFR gene a significantly shorter OS was observed HR = 3.07; p = 0.003. In multivariate analysis, significantly higher risk of death was observed in carriers of both 3R-3R genotype in TS and C-C genotype in 677C > T SNP in MTHFR HR = 3.85; p < 0.005 as well as in patients with short duration of response to first-line chemotherapy HR = 2.09; p < 0.005. Results of our study suggested that genetic factors may have a high predictive and prognostic value even greater than clinical factors for patients treated with pemetrexed monotherapy.

KeywordsNon-small cell lung cancer Pemetrexed monotherapy TS MTHFR Polymorphism  Download fulltext PDF



Author: Tomasz Kucharczyk - Paweł Krawczyk - Tomasz Powrózek - Dariusz M. Kowalski - Rodryg Ramlau - Ewa Kalinka-Warzocha - Magda

Source: https://link.springer.com/



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