title: Association of cytidine deaminase and xeroderma pigmentosum group D polymorphisms with response, toxicity, and survival in cisplatin/gemcitabine-treated advanced non-small cell lung cancer patients.
abstract: BACKGROUND
  Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non-small cell lung cancer (NSCLC). Genetic variations in drug metabolism may affect the clinical response, toxicity, and prognosis of NSCLC patients treated with cisplatin/gemcitabine-based therapy.
  
  
  METHODS
  We evaluated seven single-nucleotide polymorphisms of six genes CDA Lys27Gln (A/C); CDA C435T; ERCC1 C118T; XRCC3 Thr241Met (C/T); XPD Lys751Gln (A/C); P53 Arg72Pro (G/C), and RRM1 C524T in 192 chemotherapy-naive patients with advanced NSCLC treated with cisplatin/gemcitabine-based regimen by TaqMan probe-based assays with 7300 Real-Time PCR System, using genomic DNA extracted from blood samples.
  
  
  RESULTS
  The CDA 435 T/T genotype was significantly associated with better response (p = 0.03). The CDA 435 C/T genotype was associated with a significantly increased risk of nonhematological toxicity of grade ≥3 (p = 0.02) after adjusting for performance status, age, and type of treatment regimen. In the multivariate Cox model, the XPD 751 C/C genotype was a significant prognostic factor of longer progression-free survival (p = 0.006).
  
  
  CONCLUSIONS
  Our data suggest polymorphic variations of drug metabolic gene were associated with response and toxicity of cisplatin/gemcitabine-based therapy and progression-free survival of patients with advanced NSCLC.
authors: Medical Oncology Department, S. Maria della Misericordia Hospital, Perugia, Italy. oncolab@hotmail.com
authors: Vienna
authors: V
authors: Ludovini
authors: Irene
authors: I
authors: Floriani
authors: Lorenza
authors: L
authors: Pistola
authors: Vincenzo
authors: V
authors: Minotti
authors: Marialuisa
authors: M
authors: Meacci
authors: Rita
authors: R
authors: Chiari
authors: Daniela
authors: D
authors: Garavaglia
authors: Francesca Romana
authors: FR
authors: Tofanetti
authors: Antonella
authors: A
authors: Flacco
authors: Annamaria
authors: A
authors: Siggillino
authors: Elisa
authors: E
authors: Baldelli
authors: Maurizio
authors: M
authors: Tonato
authors: Lucio
authors: L
authors: Crinò
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003564:Cytidine Deaminase / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D003564:Cytidine Deaminase; D051759:Xeroderma Pigmentosum Group D Protein; D002945:Cisplatin; D000093542:Gemcitabine