title: Genetic variations in epigenetic genes are predictors of recurrence in stage I or II non-small cell lung cancer patients.
abstract: OBJECTIVE
  Early-stage non-small cell lung cancer (NSCLC) is potentially curable, however, many patients develop recurrent disease. Therefore, identification of biomarkers that can be used to predict patient's risk of recurrence and survival is critical. Genetic polymorphisms or single-nucleotide polymorphisms (SNP) of DNA- and histone-modifying genes, particularly those of O(6)-methylguanine DNA-methyltransferase (MGMT), have been linked to an increased risk of lung cancer as well as treatment outcomes in other tumors.
  
  
  METHODS
  We assessed the association of 165 SNPs in selected epigenetic enzyme genes, DNA methyltransferases, and methyl-CpG-binding proteins with cancer recurrence in 467 patients with stage I or II NSCLC treated with either surgery alone (N = 340) or surgery plus (neo)-adjuvant chemotherapy (N = 127).
  
  
  RESULTS
  We found several SNPs to be strongly correlated with tumor recurrence. We identified 10 SNPs that correlated with the outcome in patients treated with surgery alone but not in patients treated with surgery and adjuvant chemotherapy, which suggested that the addition of platinum-based chemotherapy could reverse the high genetic risk of recurrence. We also identified 10 SNPs that predicted the risk of recurrence in patients treated with surgery plus adjuvant chemotherapy but not in patients treated with surgery alone. The cumulative effect of these SNPs significantly predicted outcomes with P-values of 10(-9) and 10(-6), respectively.
  
  
  CONCLUSIONS
  The first set of genotypes may be used as novel predictive biomarkers to identify patients with stage I NSCLC, who could benefit from adjuvant chemotherapy, and the second set of SNPs might predict response to adjuvant chemotherapy.
authors.affiliation: Division of Cancer Medicine, and Departments of Epidemiology and Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Klaus W
authors.initials: KW
authors.lastname: Wagner
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Ara A
authors.initials: AA
authors.lastname: Vaporciyan
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins / Q000235:genetics*; D015257:DNA-Cytosine Methylases / Q000235:genetics*; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D004268:DNA-Binding Proteins; D015257:DNA-Cytosine Methylases