title: Genetic variations and patient-reported quality of life among patients with lung cancer.
abstract: OBJECTIVE
  Recent evidence has suggested a relationship between the baseline quality of life (QOL) self-reported by patients with cancer and genetic disposition. We report an analysis exploring relationships among baseline QOL assessments and candidate genetic variations in a large cohort of patients with lung cancer.
  
  
  METHODS
  QOL data were provided by 1,299 patients with non-small-cell lung cancer observed at the Mayo Clinic between 1997 and 2007. Overall QOL and subdomains were assessed by either Lung Cancer Symptom Scale or Linear Analog Self Assessment measures; scores were transformed to a scale of 0 to 10, with higher scores representing better status. Baseline QOL scores assessed within 1 year of diagnosis were dichotomized as clinically deficient (CD) or not. A total of 470 single nucleotide polymorphisms (SNPs) in 56 genes of three biologic pathways were assessed for association with QOL measures. Logistic regression with training/validation samples was used to test the association of SNPs with CD QOL.
  
  
  RESULTS
  Six SNPs on four genes were replicated using our split schemes. Three SNPs in the MGMT gene (adjusted analysis, rs3858300; unadjusted analysis, rs10741191 and rs3852507) from DNA repair pathway were associated with overall QOL. Two SNPs (rs2287396 [GSTZ1] and rs9524885 [ABCC4]) from glutathione metabolic pathway were associated with fatigue in unadjusted analysis. In adjusted analysis, two SNPs (rs2756109 [ABCC2] and rs9524885 [ABCC4]) from glutathione metabolic pathway were associated with pain.
  
  
  CONCLUSIONS
  We identified three SNPs in three glutathione metabolic pathway genes and three SNPs in two DNA repair pathway genes associated with QOL measures in patients with non-small-cell lung cancer.
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA. jsloan@mayo.edu
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
authors.forename: Mariza
authors.initials: M
authors.lastname: de Andrade
authors.forename: Paul
authors.initials: P
authors.lastname: Decker
authors.forename: Jason
authors.initials: J
authors.lastname: Wampfler
authors.forename: Curtis
authors.initials: C
authors.lastname: Oswold
authors.forename: Matthew
authors.initials: M
authors.lastname: Clark
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D011788:Quality of Life; D012189:Retrospective Studies; D018570:Risk Assessment; D012647:Self-Assessment; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D005982:Glutathione Transferase; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D025521:Tumor Suppressor Proteins; C000715087:ABCC2 protein, human; C073492:ABCC4 protein, human; C515491:MGMT protein, human; C407705:GSTZ1 protein, human