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Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients

PURPOSE: We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy. METHODS: The following polymorphisms in DNA isola...

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Autores principales: Krawczyk, Paweł, Kucharczyk, Tomasz, Kowalski, Dariusz M., Powrózek, Tomasz, Ramlau, Rodryg, Kalinka-Warzocha, Ewa, Winiarczyk, Kinga, Knetki-Wróblewska, Magdalena, Wojas-Krawczyk, Kamila, Kałakucka, Katarzyna, Dyszkiewicz, Wojciech, Krzakowski, Maciej, Milanowski, Janusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228108/
https://www.ncbi.nlm.nih.gov/pubmed/25028118
http://dx.doi.org/10.1007/s00432-014-1756-6
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author Krawczyk, Paweł
Kucharczyk, Tomasz
Kowalski, Dariusz M.
Powrózek, Tomasz
Ramlau, Rodryg
Kalinka-Warzocha, Ewa
Winiarczyk, Kinga
Knetki-Wróblewska, Magdalena
Wojas-Krawczyk, Kamila
Kałakucka, Katarzyna
Dyszkiewicz, Wojciech
Krzakowski, Maciej
Milanowski, Janusz
author_facet Krawczyk, Paweł
Kucharczyk, Tomasz
Kowalski, Dariusz M.
Powrózek, Tomasz
Ramlau, Rodryg
Kalinka-Warzocha, Ewa
Winiarczyk, Kinga
Knetki-Wróblewska, Magdalena
Wojas-Krawczyk, Kamila
Kałakucka, Katarzyna
Dyszkiewicz, Wojciech
Krzakowski, Maciej
Milanowski, Janusz
author_sort Krawczyk, Paweł
collection PubMed
description PURPOSE: We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy. METHODS: The following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5′-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3′-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations’ results were correlated with disease control rate, progression-free survival (PFS) and overall survival. RESULTS: Polymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality. CONCLUSION: The examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients.
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spelling pubmed-42281082014-11-17 Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients Krawczyk, Paweł Kucharczyk, Tomasz Kowalski, Dariusz M. Powrózek, Tomasz Ramlau, Rodryg Kalinka-Warzocha, Ewa Winiarczyk, Kinga Knetki-Wróblewska, Magdalena Wojas-Krawczyk, Kamila Kałakucka, Katarzyna Dyszkiewicz, Wojciech Krzakowski, Maciej Milanowski, Janusz J Cancer Res Clin Oncol Original Article – Cancer Research PURPOSE: We presented retrospective analysis of up to five polymorphisms in TS, MTHFR and ERCC1 genes as molecular predictive markers for homogeneous Caucasian, non-squamous NSCLC patients treated with pemetrexed and platinum front-line chemotherapy. METHODS: The following polymorphisms in DNA isolated from 115 patients were analyzed: various number of 28-bp tandem repeats in 5′-UTR region of TS gene, single nucleotide polymorphism (SNP) within the second tandem repeat of TS gene (G>C); 6-bp deletion in 3′-UTR region of the TS (1494del6); 677C>T SNP in MTHFR; 19007C>T SNP in ERCC1. Molecular examinations’ results were correlated with disease control rate, progression-free survival (PFS) and overall survival. RESULTS: Polymorphic tandem repeat sequence (2R, 3R) in the enhancer region of TS gene and G>C SNP within the second repeat of 3R allele seem to be important for the effectiveness of platinum and pemetrexed in first-line chemotherapy. The insignificant shortening of PFS in 3R/3R homozygotes as compared to 2R/2R and 2R/3R genotypes were observed, while it was significantly shorter in patients carrying synchronous 3R allele and G nucleotide. The combined analysis of TS VNTR and MTHFR 677C>T SNP revealed shortening of PFS in synchronous carriers of 3R allele in TS and two C alleles in MTHFR. The strongest factors increased the risk of progression were poor PS, weight loss, anemia and synchronous presence of 3R allele and G nucleotide in the second repeat of 3R allele in TS. Moreover, lack of application of second-line chemotherapy, weight loss and poor performance status and above-mentioned genotype of TS gene increased risk of early mortality. CONCLUSION: The examined polymorphisms should be accounted as molecular predictor factors for pemetrexed- and platinum-based front-line chemotherapy in non-squamous NSCLC patients. Springer Berlin Heidelberg 2014-07-16 2014 /pmc/articles/PMC4228108/ /pubmed/25028118 http://dx.doi.org/10.1007/s00432-014-1756-6 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Article – Cancer Research
Krawczyk, Paweł
Kucharczyk, Tomasz
Kowalski, Dariusz M.
Powrózek, Tomasz
Ramlau, Rodryg
Kalinka-Warzocha, Ewa
Winiarczyk, Kinga
Knetki-Wróblewska, Magdalena
Wojas-Krawczyk, Kamila
Kałakucka, Katarzyna
Dyszkiewicz, Wojciech
Krzakowski, Maciej
Milanowski, Janusz
Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients
title Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients
title_full Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients
title_fullStr Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients
title_full_unstemmed Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients
title_short Polymorphisms in TS, MTHFR and ERCC1 genes as predictive markers in first-line platinum and pemetrexed therapy in NSCLC patients
title_sort polymorphisms in ts, mthfr and ercc1 genes as predictive markers in first-line platinum and pemetrexed therapy in nsclc patients
topic Original Article – Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4228108/
https://www.ncbi.nlm.nih.gov/pubmed/25028118
http://dx.doi.org/10.1007/s00432-014-1756-6
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