title: Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile in head and neck squamous cell carcinomas.
abstract: BACKGROUND
  Chronic inflammation plays an important role in head and neck squamous cell carcinomas (HNSCC). This study addresses the impact of two single nucleotide polymorphisms (SNP) Asp299Gly and Thr399Ile of the toll-like receptor (TLR) 4 gene on the clinical outcome while accounting for the influence of adjuvant systemic therapy in a large cohort of HNSCC patients.
  
  
  METHODS
  Genotype analysis was done using DNA from tissue samples from 188 patients with HNSCC; TLR4 protein expression was assessed immunohistochemically in tissue microarrays. Classical survival models were used for statistical analyses.
  
  
  RESULTS
  Ten percent of patients with HNSCC presented with the TLR4 299Gly and 17% with the TLR4 399Ile allele. Patients with the heterozygous genotype TLR4 Asp299Gly had a significantly reduced disease-free and overall survival. Also, patients with the heterozygous genotype TLR4 Thr399Ile had a reduced disease-free survival. Notably, these associations seem to be attributable to relatively poor therapy response as e.g. reflected in a significantly shorter DFS among HNSCC patients carrying the Asp299Gly variant and receiving adjuvant systemic therapy.
  
  
  CONCLUSIONS
  According to this study, TLR4 299Gly und 399Ile alleles may serve as markers for prognosis of head and neck cancer in patients with adjuvant systemic therapy, particularly chemotherapy, and might indicate therapy resistance.
authors.affiliation: Department of Otorhinolaryngology, University of Duisburg-Essen, Hufelandstrasse 55, 45127 Essen, Germany. christoph.bergmann@uk-essen.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Bergmann
authors.forename: Hagen S
authors.initials: HS
authors.lastname: Bachmann
authors.forename: Agnes
authors.initials: A
authors.lastname: Bankfalvi
authors.forename: Ramin
authors.initials: R
authors.lastname: Lotfi
authors.forename: Carolin
authors.initials: C
authors.lastname: Pütter
authors.forename: Clarissa A
authors.initials: CA
authors.lastname: Wild
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Schuler
authors.forename: Jens
authors.initials: J
authors.lastname: Greve
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Hoffmann
authors.forename: Stephan
authors.initials: S
authors.lastname: Lang
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.forename: Götz F
authors.initials: GF
authors.lastname: Lehnerdt
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D012008:Recurrence; D000077195:Squamous Cell Carcinoma of Head and Neck; D016019:Survival Analysis; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4