The relationship between RRM1 gene polymorphisms and effectiveness of gemcitabine-based first-line chemotherapy in advanced NSCLC patient

R. Mlak; P. Krawczyk; Marzanna Ciesielka; Piotr Koziol; I. Homa; T. Powrózek; M. Prendecka; J. Milanowski; T. Małecka-Massalska

Ayuda

The relationship between RRM1 gene polymorphisms and effectiveness of gemcitabine-based first-line chemotherapy in advanced NSCLC patient

R. Mlak ^[1] ; P. Krawczyk ^[1] ; M. Ciesielka ^[1] ; P. Kozioł ^[1] ; I. Homa ^[1] ; T. Powrózek ^[1] ; M. Prendecka ^[1] ; J. Milanowski ^[1] ; T. Małecka-Massalska ^[1]
1. [1] Medical University of Lublin
  
  Medical University of Lublin
  
  Lublin, Polonia
Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 18, Nº. 9 (September 2016), 2016, págs. 915-924
Idioma: inglés
Texto completo no disponible (Saber más ...)
Resumen
- Purpose Chemotherapy with platinum compounds and gemcitabine is frequently used in first-line treatment of advanced non-small cell lung cancer (NSCLC) patients in which tyrosine kinase inhibitors (EGFR or ALK) cannot be administered. Unfortunately, less than half of the patients achieve the benefit from chemotherapy. Gemcitabine is an analog of deoxycytidine (pyrimidine antimetabolite) with antitumor activity. The excess of deoxycytidine synthesized by RRM1 enzyme activity may be a cause of competitive displacement of gemcitabine, which reduces the efficacy of this cytostatic. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) of the RRM1 promoter (−37C>A, −524C>T) and the effectiveness of first-line chemotherapy based on platinum compounds and gemcitabine in NSCLC patients.
  
  Patients and methods SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 91 NSCLC patients.
  
  Results The median progression-free survival (PFS) was significantly longer in carriers of AA (−37C>A) as well as CC (−524C>T) genotype of RRM1 compared to patients with other genotypes (10.5 vs 3.5 months, p = 0.0437; HR = 2.17, 95 % CI 1.02–4.62 and 10.5 vs 3.5 months, p = 0.0343; HR = 2.12, 95 % CI 1.06–4.27). In addition, the CC genotype carriers (−37C>A) showed a significant increase in the risk of shortening overall survival (OS) in comparison to patients with AA or AC genotypes (9.5 vs 18 months, p = 0.0193; HR = 2.13, 95 % CI 1.13–4.03).
  
  Conclusions Presence of rare AA (−37C>A) and CC (−524C>T) genotypes of the RRM1 may be favorable predictive factors for chemotherapy with platinum compounds and gemcitabine in NSCLC patients.