DNA hypermethylation of sirtuin 1 (SIRT1) caused by betel quid chewing-a possible predictive biomarker for malignant transformation.

BACKGROUND: DNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing. SIRT1 has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status of SIRT1 in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status of SIRT1 in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation of SIRT1 followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status of SIRT1 in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing. RESULTS: SIRT1 was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level of SIRT1 was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p < 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level of SIRT1 (p < 0.05). The methylation levels of SIRT1 in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency of SIRT1 hypermethylation (p < 0.05). CONCLUSIONS: Our results suggest that DNA hypermethylation of SIRT1 is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.

Palatal mucosal measurements in a Japanese population using cone-beam computed tomography.

STATEMENT OF THE PROBLEM: Although assessment of entire palatal mucosal thickness is important in many dental procedures, available data are mostly limited to the lateral aspect of the palate. PURPOSE OF THE STUDY: The objective of this study was to use cone-beam computed tomography (CBCT) to perform a comprehensive analysis of the palatal mucosal thickness from the gingival margin to the mid-palatine suture in a Japanese population. Associations of palatal mucosal thickness with the palatal vault depth were also examined. METHODS/MATERIALS: Measurements on the coronal plane were obtained from 44 adults with 3-mm interval in the canine (Ca), first premolar (P1), second premolar (P2), midpoint between first and second molars (M1d), first molar (M1), and second molar (M2). Furthermore, the location of greater palatine foramen (GPF) and palatine groove (PG) were also investigated. RESULTS: Canine region did not show a significant difference throughout measured points. P1, P2, and all molar regions were thickest at 9, 12, and 12 mm from the gingival margin, respectively. At 3 and 6 mm, Ca, P1, and P2 showed significantly greater thickness than the molar region. At 9 mm, P1 demonstrated a greater thickness than M1d, and P2 was greater than M1 and Mi. At 12 and 15 mm, P1 was thinner than P2, M1, and M2, whereas P2 was thinner than M2. M1 was thinner than M2. The high-vault group showed a significantly greater thickness than the low-vault group. In majority of subjects, GPF and PG were identified in second molar and first premolar to first molar, respectively. CONCLUSION: Palatal mucosa in a Japanese population was the thickest in canine to premolar regions at 9 to 12 mm from the gingival margin. Identification of GPF and PG using CBCT can assist diagnosis of palate seems to minimize surgical complications. CLINICAL SIGNIFICANCE: This study evaluated the thickness of palatal mucosa in a Japanese population using cone-beam computed tomography, covering a wide range. Canine to second premolar regions are the most suitable in harvesting palatal mucosa for the purpose of soft tissue grafts.