title: Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome in advanced non-small cell lung cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) gene intron 1 contains a polymorphic single sequence dinucleotide repeat (CA)n whose length has been found to inversely correlate with transcriptional activity. This study was designed to assess the role of (CA)n polymorphism in predicting the outcome of gefitinib treatment in advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Blood and tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were collected. EGFR intron 1 gene polymorphism, along with EGFR gene mutation, gene copy number and immunohistochemistry expression were determined. Moreover, a panel of lung cancer cell lines characterized for EGFR intron 1 polymorphism was also studied.
  
  
  RESULTS
  EGFR intron 1 polymorphism showed a statistically significant correlation with the gefitinib response (response rate 25 versus 0%, for patients with a (CA)16 and with a (CA)else genotype, respectively; p = 0.044). Patients with a (CA)16 genotype had a longer survival compared with those with a (CA)else genotype (11.4 versus 4.8 months, respectively; p = 0.037). In addition, cell lines lacking the (CA)16 allele showed a statistically significant higher IC50 compared with cell lines bearing at least one (CA)16 allele (p = 0.003).
  
  
  CONCLUSIONS
  This study supports a potential role of EGFR intron 1 polymorphism in predicting the outcome of gefitinib treatment in advanced NSCLC.
authors.affiliation: Division of Medical Oncology, University Hospital of Parma, Italy. mtiseo@ao.pr.it
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.forename: Marzia
authors.initials: M
authors.lastname: Capelletti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
authors.forename: Vittorio
authors.initials: V
authors.lastname: Franciosi
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavazzoni
authors.forename: Paola
authors.initials: P
authors.lastname: Mozzoni
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Alfieri
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.forename: Maricla
authors.initials: M
authors.lastname: Galetti
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bortesi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bozzetti
authors.forename: Maura
authors.initials: M
authors.lastname: Loprevite
authors.forename: Luca
authors.initials: L
authors.lastname: Boni
authors.forename: Roberta
authors.initials: R
authors.lastname: Camisa
authors.forename: Guido
authors.initials: G
authors.lastname: Rindi
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Petronini
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D018900:Dinucleotide Repeats / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D018628:Gene Dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D007438:Introns / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib