title: Genetic polymorphisms and treatment response in advanced non-small cell lung cancer.
abstract: BACKGROUND
  Genetic polymorphisms involved in DNA repair and apoptosis are suspected to influence patient response to cancer treatment. To evaluate the effect of genetic variations on chemotherapy and/or radiotherapy, we genotyped four single nucleotide polymorphisms (SNPs) in ATM (A60G), ERCC1 (Asn118Asn), APE1 (Asn148Glu), and iASPP (A67T), and examined their associations with treatment response among patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Included in the study were 230 patients diagnosed with inoperable advanced NSCLC. Of these patients, 76 received platinum-based chemotherapy, 125 received chemotherapy plus radiation, and 29 received radiotherapy only. The SNPs were genotyped using the TaqMan methods.
  
  
  RESULTS
  Among the patients who received chemotherapy only, ERCC1 (Asn118Asn) genotype was significantly associated with treatment response. Patients with either one or two T alleles (T/T+C/T) at Asn118Asn were more likely not to respond to platinum-based chemotherapy compared to those without the T allele (OR=4.10, 95% CI: 1.31-12.85). For patients who were treated with both chemotherapy and radiotherapy, treatment response seemed to differ substantially between patients with different genotypes of iASPP (A67T). Patients carrying an A allele (A/T+A/A) at A67T were more likely to respond to combined chemotherapy and radiotherapy compared to those not carrying the A allele (OR=0.25, 95% CI: 0.08-0.74). An association with treatment response was also suggested for the selected polymorphism in APE1, but no association was found for the ATM polymorphism.
  
  
  CONCLUSIONS
  We found that SNPs in ERCC1 and iASPP were associated with response to chemotherapy or combined chemotherapy and radiotherapy in NSCLC patients. These findings support the notion that genetic variations related to DNA repair or apoptosis may affect the effect of chemotherapy or radiation on NSCLC.
authors.affiliation: Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, 60 College Street, New Haven, CT 06520-8034, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Shenglin
authors.initials: S
authors.lastname: Ma
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Jiang
authors.forename: Wangxia
authors.initials: W
authors.lastname: Lv
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Deng
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D064007:Ataxia Telangiectasia Mutated Proteins; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018797:Cell Cycle Proteins / Q000235:genetics; D003131:Combined Modality Therapy; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C071447:ERCC1 protein, human; D004720:Endonucleases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase