title: Xeroderma pigmentosum group D haplotype predicts for response, survival, and toxicity after platinum-based chemotherapy in advanced nonsmall cell lung cancer.
abstract: BACKGROUND
  The treatment of lung cancer has reached a therapeutic plateau. Several mechanisms of platinum resistance have been described, including the removal of platinum-DNA adduct by nucleotide excision repair (NER). Polymorphisms within the Xeroderma pigmentosum Group D protein (XPD), a member of the NER pathway, are associated with alterations in enzyme activity and may change sensitivity to platinum-based chemotherapy. The authors investigated the relation between XPD polymorphisms and treatment response, toxicity, and overall survival in patients who received platinum-based chemotherapy for advanced nonsmall cell lung cancer (NSCLC).
  
  
  METHODS
  Between 2001 and 2002, 108 patients with chemotherapy-naive, advanced NSCLC were recruited. Associations between XPD312/751 polymorphisms and XPD haplotype and treatment response, toxicity. and survival were evaluated.
  
  
  RESULTS
  Significant correlations were observed between XPD haplotype and Grade 4 neutropenia and overall survival together with a greater response to platinum-based chemotherapy for the XPD *A haplotype.
  
  
  CONCLUSIONS
  The XPD haplotype may represent a useful pharmacogenomic marker of platinum-based chemotherapy in patients with advanced NSCLC and requires prospective validation.
authors.affiliation: Christie Hospital National Health Service Trust, Manchester, United Kingdom. r.booton@btopenworld.com
authors.forename: Richard
authors.initials: R
authors.lastname: Booton
authors.forename: Tim
authors.initials: T
authors.lastname: Ward
authors.forename: Jim
authors.initials: J
authors.lastname: Heighway
authors.forename: Pat
authors.initials: P
authors.lastname: Taylor
authors.forename: Fiona
authors.initials: F
authors.lastname: Power
authors.forename: Linda
authors.initials: L
authors.lastname: Ashcroft
authors.forename: Julie
authors.initials: J
authors.lastname: Morris
authors.forename: Nicholas
authors.initials: N
authors.lastname: Thatcher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D004260:DNA Repair / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D015996:Survival Rate; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D009944:Organoplatinum Compounds; D051759:Xeroderma Pigmentosum Group D Protein