title: The relationship between RRM1 gene polymorphisms and effectiveness of gemcitabine-based first-line chemotherapy in advanced NSCLC patient.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland. radoslaw.mlak@gmail.com.
authors.forename: R
authors.identifier: http://orcid.org/0000-0001-7399-8340
authors.initials: R
authors.lastname: Mlak
authors.affiliation: Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Krawczyk
authors.affiliation: Department of Forensic Medicine, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Ciesielka
authors.affiliation: Department of Forensic Medicine, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Kozioł
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.|Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Homa
authors.affiliation: Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Powrózek
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Prendecka
authors.affiliation: Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Milanowski
authors.affiliation: Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080, Lublin, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Małecka-Massalska
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D017671:Platinum Compounds; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine
keywords: Chemotherapy; Gemcitabine; Non-small cell lung cancer; Platinum compounds; RRM1