title: Effects of ERCC2 Lys751Gln (A35931C) and CCND1 (G870A) polymorphism on outcome of advanced-stage squamous cell carcinoma of the head and neck are treatment dependent.
abstract: BACKGROUND
  Germline variation in DNA damage response may explain variable treatment outcomes in squamous cell carcinoma of the head and neck (SCCHN). By grouping patients according to stage and radiation treatment, we compared SCCHN survival with regard to ERCC2 A35931C (Lys751Gln, rs13181) and CCND1 G870A (Pro241Pro, rs9344) genotypes.
  
  
  METHODS
  In a hospital-based SCCHN case series (all white, 24.7% female, mean age 58.4 years), this treatment-outcome cohort study genotyped 275 stage III-IV cases that were initially treated with radiation (with or without chemotherapy) and 80 stage III-IV and 130 stage I-II cases that were initially treated without radiation or chemotherapy and used Kaplan-Meier and Cox regression analyses to compare genotype groups on the basis of overall, disease-specific, progression-free, and recurrence-free survival rates.
  
  
  RESULTS
  ERCC2 35931 AA predicted worse survival in stage III-IV cases treated with radiation [multiply-adjusted HR = 1.66, 95% confidence interval (CI), 1.15-2.40; HR over the first 3 follow-up years = 1.92; 95% CI, 1.28-2.88] and better survival in stage III-IV cases not treated with radiation (HR = 0.26; 95% CI, 0.11-0.62). Although not associated with survival in stage III-IV cancers treated with radiation (HR = 1.00; 95% CI, 0.67-1.51), CCND1-870 GG predicted better survival in stage III-IV cancers not treated with radiation (HR = 0.14; 95% CI, 0.04-0.50). Survival in stage I-II did not depend on ERCC2 A35931C or CCND1 G870A genotype.
  
  
  CONCLUSIONS
  Although promoting tumor progression in untreated patients, germline differences in DNA-repair or cell-cycle control may improve treatment outcome in patients treated with DNA-damaging agents.
  
  
  CONCLUSIONS
  ERCC2 A35931C may help distinguish advanced stage SCCHN with better outcomes from radiation treatment.
authors: University of Pittsburgh Cancer Institute with Center for Clinical Pharmacology, Pittsburgh, PA, USA.
authors: Shilong
authors: S
authors: Zhong
authors: Tomoko
authors: T
authors: Nukui
authors: Shama
authors: S
authors: Buch
authors: Brenda
authors: B
authors: Diergaarde
authors: Lisa A
authors: LA
authors: Weissfeld
authors: Jennifer
authors: J
authors: Grandis
authors: Marjorie
authors: M
authors: Romkes
authors: Joel L
authors: JL
authors: Weissfeld
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D019938:Cyclin D1 / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human