Development Of Oral Submucous Fibrosis Research Articles

TUSC3, p53 and p21 genetic association with development of oral submucous fibrosis and oral squamous cell carcinoma among addictive tobacco chewers of Pakistan

BackgroundThis study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy’s development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF.MethodsIn this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping.ResultsThe study’s patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development.ConclusionsNotably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.

Novel Role of CD34+ Stromal Cells/Telocytes in Oral Submucous Fibrosis Development and its Malignant Transformation

BackgroundTelocytes are interstitial cells widely distributed in the extracellular matrix of numerous tissues distinguished by their long, thin, and moniliform projections. Telocytes have a role in the stimulation of angiogenesis and contribute to the development and progression of fibrosis. AimThe current study aimed to assess and compare the telocyte distribution in normal mucosa, oral submucous fibrosis (OSF), and OSCC associated with OSF (OSCC-OSF). Materials and MethodsFormalin-fixed and paraffin-embedded tissue blocks of 30 OSF cases, 15 OSCC-OSF cases, and 15 normal oral mucosae were obtained. Immunohistochemical staining was done with antibodies to CD34 to assess the vasculature and telocytes. The mean vascular density (MVD) and mean telocyte density were compared between the groups using the Kruskal-Walli test. ResultsA statistically significant high MVD (3.4 ± 1.22) and mean telocyte density (3.8 ± 1.35) was observed in OSCC-OSF cases while it was lowest in advanced OSF cases. MVD was higher in early OSF cases than in normal mucosa. ConclusionThis study showed a decrease in CD34-positive telocytes in OSF, indicating that telocyte loss promotes the development of fibrosis.Increased angiogenesis coexisted with an increase in telocytes in OSCC-OSF.

Simvastatin Attenuates Areca Nut Extract-Induced Subdermal Fibrosis in Mice by Targeting TGF-β Signaling Pathways.

Oral submucous fibrosis (OSMF) is a chronic inflammatory disease and a potentially malignant oral disorder, characterized by fibrosis of the oral mucosa. TGF-β signaling pathways have been implicated in the development of OSMF, with areca nut extract (ANE) contributing to the disease progression. Simvastatin, a statin drug, has demonstrated anti-fibrotic properties in various fibrotic conditions. However, its therapeutic potential in treating OSMF remains unclear. In this study, 8-week-old male BALB/c mice were randomly divided into three groups based on different time points. Each mouse was then treated with four different drug formulations. Post-treatment, specimens were collected for histopathological examination and staining to assess skin thickness, fibrosis, and collagen deposition. ANE treatment alone significantly increased skin thickness and collagen deposition compared to the control group after the 4-week time point. The combined administration of ANE and simvastatin, resulted in a notable reduction in skin thickness and collagen deposition. Western blot analysis revealed that simvastatin effectively suppressed the expression of fibrosis-related proteins, including CTGF, and α-SMA, in ANE-induced subdermal fibrosis. These results suggest that simvastatin has potential therapeutic effects on ANE-induced subdermal fibrosis, providing a foundation for future studies and possible clinical applications.

The mechanism of IL-13 targeting IL-13Rα2 in regulating oral mucosal FBs through PI3K/AKT/mTOR.

The objective of this investigation was to examine the presence of interleukin (IL)-13 and its receptor IL-13Rα2 in the tissues of oral submucous fibrosis (OSF), investigate their biological functions, and explore the underlying mechanisms involved in the development of OSF. The expression of IL-13 and IL-13Rα2 in the oral mucosa of patients with OSF and normal individuals was determined through immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Primary fibroblasts (FBs) were extracted through enzymatic digestion and then cultured. Immunofluorescence was employed to identify the FB cultures and the location of IL-13Rα2. The effects of IL-13/IL-13Rα2/PI3K/AKT/mTOR on the migration, proliferation, and secretion of fiber-related proteins of FBs were explored via the wound healing assay, CCK-8 assay, EDU assay, and RT-qPCR. The impact of IL-13Rα2 silencing and PI3K/AKT inhibition on the effect of IL-13 on FBs was analyzed by RT-qPCR and Western blotting. IL-13 and IL-13Rα2 were highly expressed in OSF. Primary FBs were successfully extracted and cultured. IL-13Rα2 was found to be localized in myofibroblasts. IL-13 promoted the proliferation, migration, and secretion of fibril-associated proteins in FBs. The proliferation, migration, and secretion of fibril-associated proteins of FBs were decreased following IL-13Rα2 silencing and inhibition of the PI3K/AKT/mTOR pathway. IL-13 may promote the proliferation, migration, and secretion of fiber-related proteins of FBs through the PI3K/AKT/mTOR pathway by targeting IL-13Rα2.

Chemical Composition of Areca Nut and Its Adverse Effects on Human Health.

Areca nut (AN) is one of the addictive substances consumed widely in the world. The composition of AN is very complex, and each component has variable properties. This study aimsto review the composition of AN and its adverse effects on humans. For this review, the literature search was performed by an electronic search of the Pubmed/Medline, Scopus, and Google Scholar databases using proper MESH headings and retrieved the articles published from 1997 to 2022. The eligibility criteria included human studies, a form of AN, the composition of AN, harmful effects of AN, the effect of AN on the oral cavity,the effect of AN on vital organs, and articles published in English. Data were extracted regarding the composition of AN, forms of AN, and harmful effects of AN on the oral cavity and on other systems. A total of 449 articles were identified from various databases, and 36 studies were selected that met the inclusion criteria. The active components of AN, which produce harmful effects, are primarily alkaloids, polyphenols, tannins, and certain trace elements. AN is consumed in different forms, and based on the form, its composition also varies. AN is known to cause deleterious effects on the oral cavity as well as various body organs. The most dangerous and widely reported impacts of AN on the oral cavity are the development of oral submucous fibrosis, a premalignant condition, and oral malignancy.However, during the chewing process, excretory products of AN are released and circulate in the body of "chronic habitual" and affect the other body parts. Thus, AN consumption may contribute to cardiac, liver, endocrinal, metabolic, respiratory, and reproductive system disorders also. AN composition is complex, and its consumption is harmful to human health. In regard to controlling the issue of the harmful effects of this habit, preventive measures should be established.

Knockdown of Notch Suppresses Epithelial-mesenchymal Transition and Induces Angiogenesis in Oral Submucous Fibrosis by Regulating TGF-β1.

Oral submucous fibrosis (OSF) is a chronic disorder with a high malignant transformation rate. Epithelial-mesenchymal transition (EMT) and angiogenesis are key events in OSF. The Notch signaling plays an essential role in the pathogenesis of various fibrotic diseases, including OSF. Our study aimed to explore the effects of Notch on the EMT and angiogenesis processes during the development of OSF. The expression of Notch in OSF tissues versus normal buccal mucosa samples was compared. Arecoline was used to induce myofibroblast transdifferentiation of buccal mucosal fibroblasts (BMFs). Short hairpin RNA technique was used to knockdown Notch in BMFs. Pirfenidone and SRI-011381 were used to inhibit and activate the TGF-β1 signaling pathway in BMFs, respectively. The expression of Notch was markedly upregulated in OSF tissues and fibrotic BMFs. Knockdown of Notch significantly decreased the viability and promoted apoptosis in BMFs subjected to arecoline stimulation. Downregulation of Notch also significantly suppressed the EMT process, as shown by the reduction of N-cadherin and vimentin with concomitant upregulation of E-cadherin. In addition, knockdown of Notch upregulated VEGF and enhanced the angiogenic activity of fBMFs. Moreover, inhibition of TGF-β1 suppressed viability and EMT, promoted apoptosis, and induced angiogenesis of fBMFs, while activation of TGF-β1 significantly diminished the effects of Notch knockdown on fBMFs. Knockdown of Notch suppressed EMT and induced angiogenesis in OSF by regulating TGF-β1, suggesting that the Notch-TGF-β1 pathway may serve as a therapeutic intervention target for OSF.

A Review of the Transition of Oral Keratinocytes from an Epithelial to a Mesenchymal State in Oral Submucous Fibrosis and the Potential Function of Apamin in Reversing This Transition

Epithelial–mesenchymal transition (EMT) causes polarized and cohesive epithelial cells to become motile and join the extracellular matrix (ECM). Embryonic development, wound healing, and tissue repair need it. Interestingly, the same mechanism may cause cancer, organ fibrosis, scarring, and organ failure. WNT, Notch, Hedgehog, and RTK signaling impact EMT. This process also includes nontranscriptional changes due to growth hormones, cytokines, hypoxia, and ECM interaction. The reason for the development of oral submucous fibrosis (OSF) is believed to be multifaceted; nevertheless, there is substantial evidence supporting the notion that it arises from dysregulation of collagen. EMT is a prominent phenomenon in the development of OSF, whereby myofibroblasts and keratinocytes are the cells most affected. The role of EMTs is crucial in both physiological and pathological processes. The significance of EMT involvement in the pathogenesis of OSF and the preceding inflammatory response suggests a promising avenue for further investigation. Transforming growth factor-1 (TGF-1) plays a crucial role in the EMT of oral keratinocytes that initiates the pathogenesis of OSF. The objective of this review is to analyze the events of EMT in OSF, along with the processes and molecular routes that regulate alterations in gene expression within the oral cavity. The potential for cancerous transformation is linked to OSF, prompting an examination of the involvement of apamin in the advancement of EMT triggered by TGF-1 in oral keratinocytes.

Influence of smokeless tobacco in development of oral submucous fibrosis among industrial workers: A cross-sectional study

Background: Tobacco usage in any form can contribute toward the development of various precancerous and cancerous lesions. Oral submucous fibrosis (OSMF) is a chronic precancerous lesion which has the highest rates of malignant transformation. Therefore, the present study was conducted among industrial workers to observe the effect of various forms of smokeless tobacco (SLT) usage and development of OSMF. Materials and Methods: The present cross-sectional study was conducted among 3998 industrial after obtaining approval from concerned authorities. A self-administered questionnaire approved by specialists was used to collect data from the study participants. The clinical diagnosis (the presence of fibrous bands and blanching) was performed by trained examiners who were calibrated in the department. Mouth opening was recorded by Vernier caliper. Statistical analysis was done using the Chi-square test and statistical significance was set at P ≤ 0.05. Results: The mean age of the study population was 38.341 ± 9.89 years. OSMF was reported in 50.2% (1149) of participants who were consuming one or other forms of SLT. Fibrous bands were seen in 59.6% of participants chewing areca nut, 56.8% of participants who consumed pan masala, and 50.6% of participants consuming khaini. 48.9% of participants who chewed gutkha developed blanching over their intraoral mucosa. Fibrous bands and blanching of the oral mucosa were observed in 89.4% and 88.3% of participants, respectively, who consumed all four types of SLT. Conclusion: Consumption of SLT has a strong correlation with the development of OSMF, especially with the use of gutkha, pan masala, and khaini. There is a need for public education programs among such vulnerable population groups.

The Antioxidant Effects of Sesamol on Bleomycin-Induced Oral Submucous Fibrosis

Objective: Oral submucous fibrosis (OSF) is a disease characterized by abnormal collagen deposition that causes inflammation and malignancy in oral mucosal tissue. Fibroblasts and myofibroblasts, are the cells that show significant activation in the development of OSF. Bleomycin (BL) is a chemotherapeutic agent commonly used in cancer treatment that also causes inflammatory changes in the oral mucosa, initiating fibrosis in the oral submucosal tissue. Sesamol (SE) has antioxidative and anti-inflammatory properties which are abundant in sesame seeds and sesame oil, and SE has a beneficial effect on the mucosal layer. This experimental study aimed to investigate SE’s effects on BL-induced OSF. Materials and Methods: The study obtained 18 healthy adult male albino rats aged 3-4 months and weighing 200-250g from Bolu Abant Izzet Baysal University’s Experimental Animal Application and Research Center. The rats were divided randomly into control, BL, and BL + SE groups (n = 6 in each group). A model of OSF was established in the rats by administering 0.5 mg/mL of BL and 50 mg\kg of SE to the BL+SE group each day. The hematoxylin and eosin stain and Masson’s trichrome stain were used to assess histopathological changes in the oral mucosa. Results: The results revealed SE to have beneficial effects on BL-induced OSF through its antioxidant and anti-inflammatory properties. Histopathological evaluations and biochemical analysis of oral submucosal tissue samples also revealed SE to provide statistically significant protection against fibrosis in the oral mucosa (p < 0.01). Conclusion: This study has demonstrated oral submucous fibrosis that develops due to BL as well as SE to have an antioxidant effect on OSF regarding BL-induced reactive oxygen species (ROS) activation and collagen synthesis.

Are There Betel Quid Mixtures Less Harmful than Others? A Scoping Review of the Association between Different Betel Quid Ingredients and the Risk of Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g., areca nut, betel leaves), with or without smokeless tobacco. BQ ingredients contain pro-carcinogenic bioactive compounds, but also potentially protective biomolecules, and we have shown recently that the chemical properties of different BQ recipes vary, which may explain the unequal prevalence of OSF and oral cancer in BQ users in different geographical regions. Hence, this scoping review was aimed at evaluating the existing literature regarding different BQ compounds and their association with OSF. The repository of the National Library of Medicine (MEDLINE/PubMed), medRxiv databases, Google scholar, Baidu scholar, CNKI, and EBSCO were used to search for publications that investigated the association between BQ chewing and OSF up to November 2021. The search terminology was constructed using the keywords “betel quid” and “oral submucous fibrosis”, and their associated terms, with the use of Boolean operators. The search was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, together with clear inclusion and exclusion criteria. The review showed that the risk of developing OSF varied between different BQ recipes, and that chewing BQ mixtures containing betel inflorescence (BI) significantly increased the risk of OSF, as did the addition of tobacco. Conversely, the use of betel leaf in the mixture was likely to be protective, which may be due to the presence of polyphenols. Although further research is needed to determine the effect of individual BQ ingredients in the development of OSF, our pilot results provide the scope and rationale for informing future chemopreventive strategies for OSF and oral cancer in BQ chewers.

Tyrosine sulphation of CXCR4 induces the migration of fibroblast in OSF.

Oral submucous fibrosis (OSF) caused by areca nut chewing is a prevalent fibrotic disease in Asia-Pacific countries. Arecoline-induced migration of fibroblasts (FBs) plays a vital role in the development of OSF. However, the specific molecular mechanisms involved remain unclear. Many studies have shown that tyrosine sulphation of chemokines can influence cell migration. Herein, we demonstrated that arecoline stimulates tyrosine sulphation of the chemokine receptor 4 (CXCR4) through the tyrosylprotein sulphotransferase-1 (TPST-1) to enhance the migration ability of FBs. Moreover, by RNA-Seq analysis, we found that the most significantly altered pathway was the EGFR pathway after the arecoline stimulation for FBs. After the knockdown of arecoline-induced EGFR expression, the tyrosine sulphation of CXCR4 was significantly decreased by the inhibition of TPST-1 induction. Finally, in human OSF specimens, TPST-1 expression was directly correlated with the expression of CXCR4. These data indicate that the arecoline-induced tyrosine sulphation of CXCR4, which is regulated by TPST-1, might be a potential mechanism that contributes to FB migration in OSF.

An Account of Areca Nut Uses and Oral Health Damages from An Indian Perspective

There is a perception in India that packaged paan masala and betel quid (BQ) with areca nut loosely called paan supari both being devoid of tobacco are not carcinogenic. This article intends to be an awareness initiative against this notion. It focuses on the use of areca nuts in various forms. An understanding is necessary for the identification of components of gutka, various forms of BQ, and paan masala wherein areca nut is used. Areca nut consumption damages oral health and leads to the development of oral submucous fibrosis (OSF). OSF is used as an umbrella term for depicting all potentially malignant lesions. Gutka is a product popular in India that uses areca nuts and a form of flavoured tobacco (zarda) as the main component. Although oral tobacco is implicated as a grade I carcinogen, areca nuts and BQ-containing areca nuts belong to the same grade. Areca nuts are the fourth largest addictive substance in the world. Deleterious effects of areca nuts in various forms are a grossly underreported area of research. Initiatives against areca nut uses are required.

English

BACKGROUND Oral submucous fibrosis (OSMF) is the most common precancerous lesion, prevalent mostly in South East Asia. The habit of betel nut or gutkha chewing is the main cause for this. There is a direct association between gutkha chewing habit and development of OSMF, the reason being exaggerated forces on the masseter muscle due to vigorous chewing for prolonged period of time. So, the present study was done to evaluate the thickness of masseter muscle in OSMF patients. METHODS A total of 25 subjects were included in the study from January 2015 to December 2017. 25 OSMF patients belonging to the age group of 25-50 years who attended the outpatient department of Veer Surendra Sai Medical College and Hospital, Burla, with masseteric hypertrophy and betelnut or gutkha chewing habit for more than 5 years, were included in the study. The computed tomography (CT) scans were obtained using Siemens Somatom Sensation 4-slice CT scanner. During the scanning period, the patients were asked to keep their mouth gently closed and relaxed. Axial sections of the CT scans were assessed for masseter muscles. The thickness of the muscle was calculated using image-analysing software and the measurements made were in millimeter (mm). Tabulation was done and statistical analysis was done using Mann-Whitney U test. RESULTS The thickness of masseter muscle of right side was found to be more than the left side in all patients except for one patient and the outcome was statistically significant with one tailed p value < 0.01. CONCLUSIONS The duration and frequency of the habit were found to be directly proportional to masseter muscle thickness and also with the clinical progression of the disease. Similarly, we also concluded from our study that there exists an association of masseter muscle hypertrophy with OSMF, and CT scan meas KEYWORDS OSMF, Masseter Muscle, CT Scan

Arecoline enhances miR-21 to promote buccal mucosal fibroblasts activation

Oral submucous fibrosis (OSF) is an irreversible fibrosis disease and a potentially malignant disorder in the oral cavity. Various studies have shown that miR-21 was implicated in the fibrogenesis and carcinogenesis, but its functional role in the development of OSF has not been investigated. The expression levels of miR-21 in arecoline-stimulated normal buccal mucosal fibroblasts (BMFs) and OSF specimens were determined by qRT-PCR. Exogenous administration of TGF-β and its inhibitor (SB431542) were utilized to examine the involvement of TGF-β signaling in miR-21 alteration. Collagen gel contraction, transwell migration, and invasion assays were used to assess the myofibroblast activities. The relationship between α-SMA and miR-21 was calculated using the Pearson correlation coefficient. MiR-21 expression was induced in BMFs by arecoline treatment in a dose-dependent manner. Our results showed that this upregulation was mediated by TGF-β signaling. Subsequently, we demonstrated that the administration of the miR-21 inhibitor suppressed the arecoline-induced myofibroblast characteristics, including a higher collagen gel contractility and cell motility, in normal BMFs. Furthermore, inhibition of miR-21 was sufficient to attenuate the myofibroblast features in fibrotic BMFs. Besides, we showed that the expression of miR-21 was aberrantly upregulated in the OSF tissues and there was a positive correlation between miR-21 and myofibroblast marker, α-SMA. MiR-21 overexpression in OSF may be due to the stimulation of areca nut, which was mediated by the TGF-β pathway. Our data suggested that the repression of miR-21 was a promising direction to palliate the development and progression of OSF.

Distinct phenolic, alkaloid and antioxidant profile in betel quids from four regions of Indonesia

Betel quid (BQ) is a chewing mixed package that mainly contains areca nut (AN), betel leaf (Leaf) or betel stem inflorescence (SI), and slaked lime, and is consumed with or without tobacco BQ chewing is common in South East Asia and has been strongly associated with malignant and potentially malignant diseases of the oral cavity. Alkaloids such as arecoline are often accounted for the carcinogenic potential of BQ, however the chemical composition of BQ has not been studied in detail. In the current study, we investigated the total phenolic content (TPC), antioxidant activity (by mean of ferric reducing antioxidant power, FRAP), radical scavenging activity (DPPH test), polyphenolic profile and arecoline content in different components of BQ, namely AN, Leaf or SI, Husk, and blended BQ (BQ mix, containing AN, Leaf or SI and slaked lime). Samples were imported from 4 major regions of Indonesia, namely: Banda Aceh (BA), North Sumatra (NS), West Kalimantan (WK) and West Papua (WP). The highest TPC, FRAP, and DPPH values were detected in AN samples compared to other BQ components, while samples from WP region were of higher values compared to the other regions. High performance liquid chromatography—Mass Spectrometry (LC–MS) analysis showed that Husk contains the widest range of polyphenols, including hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols and stilbenes. Catechin and epicatechin were the main polyphenols detected in BQ, and they were present at the highest concentrations in WP–AN sample. Arecoline was detected in all AN and BQ mix samples and was significantly correlated with catechin and epicatechin, and significantly negatively correlated with p-hydroxybenzoic acid. Notably, arecoline concentration changed significantly when AN was blended in BQ mixtures. The current study is the first to extensively characterise the chemical composition of BQ and provides insight for a better understanding of the interactions of BQ alkaloids and phenolics in the development of oral submucous fibrosis and oral cancer.

A Review on Role of Arecoline and Its Metabolites in the Molecular Pathogenesis of Oral Lesions with an Insight into Current Status of Its Metabolomics.

Areca nut consumption is a popular habit in Southeast Asian countries. One of the important biologically active alkaloids of areca nut is arecoline, which plays a role in mediating the development of several pathologies of the primary exposure site, the oral cavity. Studies on the metabolism of arecoline revealed the formation of several metabolites which themselves might be toxic. Moreover, polymorphisms in genes encoding enzymes involved in the metabolism of arecoline might predispose an organism towards the development of oral cancer. The present review tries to accumulate all the relevant existing literature and then elucidate the molecular mechanism by which arecoline plays a role in the development of oral submucous fibrosis and oral cancer. Existing information regarding arecoline metabolism, enzymes involved in the metabolic process and biological effects of the metabolites of arecoline have also been compiled and compared to study the toxicity of metabolites with its parent compound arecoline and whether they play any role in the pathogenesis of oral cancer mediated by areca nut consumption. A repertoire of molecular targets has come up in the discussion whose expression profile is perturbed by arecoline. Construction of induction cascade from existing literature has given an idea about the process of molecular pathogenesis. The summarized and analysed data can help to determine the molecular mechanism and drug targets, which in turn could be helpful in the prevention or treatment of these pathological conditions. It also brings into light areas where further research needs to be directed.

Patterns of Tobacco Use and its Relation to Oral Precancers and Cancers among Individuals Visiting a Tertiary Hospital in South India

The aim of this study was to evaluate the use of tobacco and its association with oral precancers and cancers. Medical records of 1,007 individuals were assessed for the patterns of tobacco abuse and the presence of tobacco-related oral mucosal alterations. This study comprised 1,007 individuals (M:F: 95.4%:4.6%). In the cohort, 60.1% had smoking habit and 56.1% had smokeless habit. Of the bidi smokers, 18.2% developed carcinoma, 14.3% developed leukoplakia, which is statistically significant (p < 0.001). A logistic regression analysis of the development of oral submucous fibrosis (OSMF) shows that habit of smokeless forms of tobacco has an odds ratio (OR) of 18+ when compared with smoking. Combination of bidi and gutkha had 12.3 times higher risk of developing oral cancer and 4.4 times risk of developing leukoplakia. A total of 33.3% betel quid and gutkha chewers presented with tobacco pouch keratosis, which is statistically significant. Smoked and smokeless forms of tobacco were equally popular among the study population. The packeted form of smokeless tobacco (gutkha) was more prevalent. Oral submucous fibrosis was more common than leukoplakia, and oral cancer developed more frequently in elderly men smoking bidis. This study throws light on the fact that the use of both smoke and smokeless forms of tobacco is still prevalent, and the use of gutkha was most prevalent. These findings will help tobacco cessation and counseling centers to focus their effort in motivating people to stop gutkha chewing habit. This also brings to the forefront the need to create better treatment strategies to manage OSMF.

Assessment of Effects of Areca Nut in the Development of Oral Sub-mucous Fibrosis amongst Nursing Students

Assessment of Effects of Areca Nut in the Development of Oral Sub-mucous Fibrosis amongst Nursing Students

Molecular pathways regulated by areca nut in the etiopathogenesis of oral submucous fibrosis

Many oral mucosal lesions are due to substance abuse, such as tobacco and areca nut, amongst others. There is considerable evidence that oral lesions/disorders such as some leukoplakias, most erythroplakias, and submucous fibrosis have malignant potential, with a conversion rate of 5%-10% over a 10-year period. There have been several reports on possible biomarkers that predict malignant conversion of the oral lesions associated with these disorders. Management of these is mostly surgical removal of the lesion followed by observation, and in some cases treatment by antioxidants and anti-inflammatory agents. Oral submucous fibrosis is due to excessive deposition of extracellular matrix in the connective tissue plus, particularly, collagens. The deposition of collagen leads to stiffness of the affected regions and results in difficulty in mouth opening. Areca nut chewing is proposed as the most probable etiological factor in the manifestation of oral submucous fibrosis. Several studies suggest involvement of proinflammatory cytokines, dysregulated by areca nut, in the development of the disease. Amongst these, transforming growth factor-β is in the forefront, which is also shown to be involved in fibrosis of other organs. This review addresses the molecular mechanisms involved in oral submucous fibrosis development and provides a model for the regulation of transforming growth factor-β by areca nut. It provides an exemplar of the role of modern molecular techniques in the study of oral disease.

Alteration of the risk of oral pre-cancer and cancer in North Indian population by XPC polymorphism genotypes and haplotypes

Chewing and smoking of tobacco have been reported to cause DNA damage in oral mucosa which can be repaired by Xeroderma Pigmentosum Group C (XPC) protein. This study aimed to evaluate the association of XPC gene polymorphisms with the risk of oral diseases including oral pre cancer and cancer. In the present study we genotyped 302 patients with oral diseases and 300 healthy controls for XPC PAT (D > I), C > T and A > C polymorphisms with PCR-RFLP and PCR method. Haplotypes were constituted from different XPC genotypes with SNPstats programme. Our results show that individuals with D/I genotype for XPC D > I polymorphism were significantly protected from developing Oral submucous fibrosis (OSMF) and Leukoplakia (p = .029 and 0.031 and respectively). Risk of oral cancer was also significantly lower with the I/I genotype of the same XPC polymorphism (p = .048). However, once oral cancer is established, individual with I allele were at significantly increased risk for having high stage and metastatic tumor (p = .011 and 0.03 respectively). Carrier of T allele for XPC C > T polymorphism were significantly protected from development of OSMF (p = .004) but did not show any association with the development of other pre oral cancerous lesions or oral cancer. In contrast, CC genotype as well as C allele for XPC A > C polymorphism was significantly associated with increased risk of Lichenplanus (p = .006 and 0.004 respectively). XPC C > T and A > C polymorphisms did not show any association with clinical parameters of oral cancer. Haplotype D/T/A and I/T/A showed protective association with development of oral disease (P-value = .001 and 0.0001 respectively). In conclusion, results from the present study demonstrate association of XPC polymorphisms with oral pre cancer and cancer.