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Author Notes:

Johann C Brandes, M.D., PhD, Atlanta Veterans Affairs Medical Center, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, johann.brandes@emory.edu

JCB had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Authors reported no conflicts of interest.


Research Funding:

This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development” (Biomedical Laboratory Research and Development)-7IK 2BX001283-02 to JCB.

Other grant funding includes: NCI- 5 P50 CA128613-02 Career Development Project to JCB; NCI-P30CA138292 pilot grant to JCB; CHEST Foundation/Lungevity Foundation Clinical Lung Cancer Research award to JCB; Uniting against Lung Cancer /Lungevity Foundation research award to JCB; Suntrust Scholar Award to JCB.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • histone deacetylase (HDAC) inhibition
  • valproic acid
  • DNA methylation
  • squamous cell carcinoma
  • head and neck cancer

Long-term use of valproic acid in US veterans is associated with a reduced risk of smoking-related cases of head and neck cancer


Journal Title:



Volume 120, Number 9


, Pages 1394-1400

Type of Work:

Article | Post-print: After Peer Review


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.

Copyright information:

© 2013 American Cancer Society.

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