title: Single nucleotide polymorphisms in tobacco metabolism and DNA repair genes and prognosis in resected non-small-cell lung cancer.
abstract: BACKGROUND
  If tobacco-related carcinogens are not inactivated or extruded from the cell, they can damage the DNA. Single nucleotide polymorphisms (SNPs) in genes involved in tobacco metabolism, DNA repair, and multidrug resistance have been related to lung cancer susceptibility. We examined 13 SNPs in 10 of these genes and correlated the results with time to progression (TTP) and overall survival (OS) in 71 smoker or former smoker patients with resected non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  DNA was obtained from paraffin-embedded tumor. SNP analysis of the candidate genes was performed by allelic discrimination assay. Log-rank test, Kaplan-Meier plots, and Cox multivariate analysis were used to evaluate the association of TTP and survival with the SNPs evaluated.
  
  
  RESULTS
  Patients with wild-type (wt) XPC rs2228001, wt CYP2C8 rs10509681, or non-wt NAT2 rs1799930 had a longer TTP. Patients with wt ERCC1 showed a nonsignificant trend towards longer TTP. No other relation between SNPs and TTP were observed. Patients harboring at least two unfavorable genotypes in these four genes had a shorter TTP and OS than patients with either one or no unfavorable genotypes. In the multivariate analysis, non-wt XPC rs2228001 and the presence of at least two unfavorable genotypes emerged as independent markers for shorter TTP.
  
  
  CONCLUSIONS
  SNPs in tobacco metabolism and DNA repair genes may influence the clinical outcome of resected NSCLC.
authors.affiliation: Department of Medical Oncology, ICMHO, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Campayo
authors.forename: Nuria
authors.initials: N
authors.lastname: Viñolas
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.forename: Enric
authors.initials: E
authors.lastname: Carcereny
authors.forename: Francesc
authors.initials: F
authors.lastname: Casas
authors.forename: Bernat
authors.initials: B
authors.lastname: Gel
authors.forename: Tania
authors.initials: T
authors.lastname: Diaz
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Gimferrer
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Marrades
authors.forename: Jose
authors.initials: J
authors.lastname: Ramirez
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000601:surgery*; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm