TY - JOUR
T1 - Long-term use of valproic acid in US veterans is associated with a reduced risk of smoking-related cases of head and neck cancer
AU - Kang, Hyunseok
AU - Gillespie, Theresa W.
AU - Goodman, Michael
AU - Brodie, Seth A.
AU - Brandes, Mina
AU - Ribeiro, Maria
AU - Ramalingam, Suresh S.
AU - Shin, Dong M.
AU - Khuri, Fadlo R.
AU - Brandes, Johann Christoph
PY - 2014/5/1
Y1 - 2014/5/1
N2 - 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. Cancer 2014;120:1394-1400.
AB - 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. Cancer 2014;120:1394-1400.
KW - DNA methylation
KW - head and neck cancer
KW - histone deacetylase (HDAC) inhibition
KW - squamous cell carcinoma
KW - valproic acid
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U2 - 10.1002/cncr.28479
DO - 10.1002/cncr.28479
M3 - Article
C2 - 24664792
AN - SCOPUS:84899478904
SN - 0008-543X
VL - 120
SP - 1394
EP - 1400
JO - Cancer
JF - Cancer
IS - 9
ER -