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Forty-two active or former smokers were included in this randomized, double-blind, placebo-controlled trial. Oral rinse samples were collected prior to treatment with valproic acid or placebo and after 90\u00a0days of treatment. The methylation status of five tumor suppressor genes and histone acetylation were evaluated by pyrosequencing and ELISA techniques, respectively. Differences between the 90-day and baseline oral rinse acetylation and methylation results were analyzed by comparing groups. Thirty-four patients were considered for analysis. The mean percentage adherence in the valproic and placebo groups was 93.4 and 93.0, respectively (p\u2009=\u20090.718). There was no statistically significant difference between groups when comparing the medians of the histone acetylation ratio and the methylation ratio for most of the studied genes. A significant reduction in the <jats:italic>DCC<\/jats:italic> methylation pattern was observed in the valproic group (p\u2009=\u20090.023). The use of valproic acid was safe and accompanied by good therapeutic adherence. <jats:italic>DCC<\/jats:italic> methylation was lower in the valproic acid group than in the placebo group.<\/jats:p>","DOI":"10.1038\/s41598-021-95845-3","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:03:40Z","timestamp":1628762620000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of acetylation and methylation in oral rinse of patients with head and neck cancer history exposed to valproic acid"],"prefix":"10.1038","volume":"11","author":[{"given":"Ricardo Ribeiro","family":"Gama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia Maria Rebolho Batista","family":"Arantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Pereira","family":"Sorroche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"De Marchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matias Eliseo","family":"Melendez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raiany Santos","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos Alves","family":"de Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Luiz","family":"Vettore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Lopes","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"95845_CR1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394\u2013424. https:\/\/doi.org\/10.3322\/caac.21492 (2018).","journal-title":"CA Cancer J. Clin."},{"key":"95845_CR2","unstructured":"Wild, C. P., Weiderpass, E. & Stewart, B. W. World Cancer Report: Cancer Research for Cancer Prevention. http:\/\/publications.iarc.fr\/586 (2020).  (Accessed 01 Oct 2020)."},{"key":"95845_CR3","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1186\/s12885-018-4806-7","volume":"18","author":"L Zhong","year":"2018","unstructured":"Zhong, L. et al. Biomarkers: Paving stones on the road towards the personalized precision medicine for oral squamous cell carcinoma. 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