Department of Oncology, Johns Hopkins University, Baltimore, Maryland.
Cancer. 2014 May 1;120(9):1394-400. doi: 10.1002/cncr.28479. Epub 2014 Mar 24.
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.
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.
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).
Use of VPA is associated with a lower risk of developing head and neck cancers.
表观遗传事件在与烟草相关的癌症的致癌过程中起着重要作用。作者进行了一项回顾性队列研究，以评估抗惊厥药物丙戊酸（VPA），一种组蛋白去乙酰化酶抑制剂，暴露于发展为肺癌、头颈部癌、前列腺癌、膀胱癌和结肠癌的风险。
该研究基于 2002 年至 2008 年国家退伍军人事务部（VA）医疗 SAS 数据集与 VA 中央癌症登记处相关联。队列定义为年龄>40 岁的患者，他们在 VA 系统中至少随访 1 年，用于存在 VPA 适应证的 4 种诊断之一（双相情感障碍、创伤后应激障碍、偏头痛和癫痫发作）。多变量 Cox 比例风险模型用于估计危险比（HR）和 95%置信区间（95%CI），反映 VPA 使用与癌症发病率之间的关联。
VPA 的使用与头颈部癌症风险的显著降低相关（HR，0.66；95%CI，0.48-0.92）。还观察到与治疗持续时间和中位 VPA 药物水平相关的额外关联。肺癌（HR，1.00；95%CI，0.84-1.19）、膀胱癌（HR，0.86；95%CI，0.64-1.15）、结肠癌（HR，0.95；95%CI，0.74-1.22）和前列腺癌（HR，0.96；95%CI，0.88-1.12）的癌症发病率无显著差异。
VPA 的使用与发展为头颈部癌症的风险降低相关。
