title: Long-term use of valproic acid in US veterans is associated with a reduced risk of smoking-related cases of head and neck cancer.
abstract: BACKGROUND
  Epigenetic events play a major role in the carcinogenesis of tobacco-related cancers. The authors conducted a retrospective cohort study to evaluate the effects of exposure to the anticonvulsant agent valproic acid (VPA), a histone deacetylase inhibitor, on the risk of developing cancers of the lung, head and neck, prostate, bladder, and colon.
  
  
  METHODS
  The study was based on the 2002 through 2008 National Veterans Affairs (VA) medical SAS data set linked to the VA Central Cancer Registry. The cohort was defined as subjects aged>40 years who were followed in the VA system for at least 1 year for 1 of 4 diagnoses for which a VPA indication exists (bipolar disorder, posttraumatic stress disorder, migraines, and seizures). Multivariable Cox proportional hazards models were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CI) reflecting the association between use of VPA and cancer incidence.
  
  
  RESULTS
  VPA use was associated with a significant reduction in the risk of cancers of the head and neck (HR, 0.66; 95% CI, 0.48-0.92). Additional associations were noted with the duration of treatment and median VPA drug levels. No significant differences in cancer incidence were observed for cancers of the lung (HR, 1.00; 95% CI, 0.84-1.19), bladder (HR, 0.86; 95% CI, 0.64-1.15), colon (HR, 0.95; 95% CI, 0.74-1.22), and prostate (HR, 0.96; 95% CI, 0.88-1.12).
  
  
  CONCLUSIONS
  Use of VPA is associated with a lower risk of developing head and neck cancers.
authors.affiliation: Department of Oncology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Kang
authors.forename: Theresa W
authors.initials: TW
authors.lastname: Gillespie
authors.forename: Michael
authors.initials: M
authors.lastname: Goodman
authors.forename: Seth A
authors.initials: SA
authors.lastname: Brodie
authors.forename: Mina
authors.initials: M
authors.lastname: Brandes
authors.forename: Maria
authors.initials: M
authors.lastname: Ribeiro
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: Johann Christoph
authors.initials: JC
authors.lastname: Brandes
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D015331:Cohort Studies; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012306:Risk; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014481:United States; D014635:Valproic Acid / Q000008:administration & dosage* / Q000097:blood; D014728:Veterans / Q000706:statistics & numerical data*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid; D051548:Histone Acetyltransferases
keywords: DNA methylation; head and neck cancer; histone deacetylase (HDAC) inhibition; squamous cell carcinoma; valproic acid