Deepika Shukla

Genetic polymorphism of drug metabolizing enzymes (GSTM1 and CYP1A1) as risk factors for oral premalignant lesions and oral cancer

AIMS Polymorphisms in the genes that code for metabolic enzymes involved in either the activation (Phase I) or detoxication (Phase II) of chemical carcinogens in tobacco, may alter expression or function of carcinogenic compounds and hence alter risk of oral cancer. The present study investigates whether polymorphisms at CYP1A1 and GSTM1 gene loci act as risk factors for oral precancerous lesions and cancer. METHODS For the present study, histopathologically confirmed cases of 90 oral precancerous lesions, 150 oral squamous cell carcinoma (SCC) and 150 control subjects were selected. Polymerase chain reaction and restriction fragment length polymorphism were performed using DNA from blood samples to determine the polymorphic genotypes at CYP1A1 and GSTM1 loci. RESULTS CYP1A1 C (m2/m2) genotype conferred a 12.0 fold-increased risk (OR=12.0; 95% CI, 2.40-60.05) to oral SCC. GSTM1 null showed no significant association but the frequency was higher in oral SCC cases. Patients with genotype C and/or GSTM1 deficiency developed carcinoma after less tobacco consumption than those of other genotypes though the difference was not statistically significant. The frequency of the combined genotypes C and GSTM1 null was found to be 14% among oral SCC patients. On comparing the susceptibility of intraoral sites it was found that in the majority of cases (64%) in the study groups they were the buccal mucosa. CONCLUSION Hence it was concluded that metabolic enzymes reported in the present study: CYP1A1 significantly alter oral cancer risk. GSTM1 null and CYP1A1 C (m2m2) show a predisposition to premalignant lesions and cancer of the buccal mucosa than other sites.

Expression of transforming growth factor β and its correlation with lipodystrophy in oral submucous fibrosis: an immunohistochemical study.

Objective: In our routine review of Oral Submucous Fibrosis (OSMF) biopsies, we observed decreased adipose tissue even though most are from buccal mucosa. Pathogenesis of OSMF has demonstrated the role of Transforming Growth Factor β (TGF β), in causing fibrosis. This study aims to correlate the role of TGF β with loss of adipose tissue in OSMF. Study Design: From our archives, 84 OSMF cases (24 early and 60 advanced OSMF) were screened for adipose tissue. Immunoexpression of TGF β in these cases were investigated. Results: Adipose tissue was seen in 67% of early OSMF and in 13% of advanced cases. Early cases showed more intense TGF β staining of epithelium, fibroblast, macrophages and inflammatory cells than the advanced cases. Conclusion: These findings suggest that TGF β plays a key role in causing lipodystrophy in OSMF and is secreted more during early course of the disease than in advanced stage. Key words:Adipose tissue, oral submucous fibrosis (OSMF), transforming growth factor β (TGF β), lipodystrophy.

Dentofacial and Cranial Changes in Down Syndrome

Objectives This study aimed to determine the prevalence of certain oral characteristics usually associated with Down syndrome and to determine the oral health status of these patients. Methods The cross-sectional study was conducted among patients attending a special education program at Faculty of Dentistry, Jamia Millia Islamia, Delhi, India. The study design consisted of closed-ended questions on demographic characteristics (age, sex, and education and income of parents), dietary habits, and oral hygiene habits. Clinical examination included assessment of oral hygiene according to Simplified Oral Hygiene Index (OHI-S), dental caries according to decayed, missing, and filled teeth (DMFT) index, periodontal status according to the Community Periodontal Index of Treatment Needs (CPITN), and malocclusion according to Angles classification of malocclusion. Examinations were carried out using a using a CPI probe and a mouth mirror in accordance with World Health Organization criteria and methods. Craniometric measurements, including maximum head length and head breadth were measured for each participant using Martin spreading calipers centered on standard anthropological methods. Results The majority of the patients were males (n = 63; 82%) with age ranging from 6–40 years. The Intelligence Quotient (IQ) score of the patients indicated that 31% had moderate mental disability and 52% had mild mental disability. 22% exhibited hearing and speech problems.12% had missing teeth and 15% had retained deciduous teeth in adult population. The overall prevalence of dental caries in the study population was 78%. DMFT, CPITN and OHI scores of the study group were 3.8 ± 2.52, 2.10 ± 1.14 and 1.92 ± 0.63 respectively. The vast majority of patients required treatment (90%), primarily of scaling, root planing, and oral hygiene education. 16% of patients reported CPITN scores of 4 (deep pockets) requiring complex periodontal care. The prevalence of malocclusion was 97% predominantly of Class III malocclusions. Further 14% presented with fractured anterior teeth primarily central incisor. The percentage means of cephalic index was 84.6% in the study population. The brachycephalic and hyperbrachycephalic type of head shape was dominant in the Down syndrome individuals (90%). Conclusion The most common dentofacial anomaly seen in these individuals was fissured tongue followed by macroglossia.

Can Quantifying Free-Circulating DNA Be a Diagnostic and Prognostic Marker in Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma?

PURPOSE Previous studies have reported significantly higher concentrations of serum DNA in various types of cancers. Thus the study aims to determine whether circulating free DNA (CFDNA) can aid in the diagnosis and prognosis of oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS A nonrandomized case-control study was planned where cases were derived from patients who presented to the KLE Institute of Dental Sciences, Belgaum, India, for evaluation and management of oral lesions between 2007 and 2009. In this study the predictor variable was status of the disease in the patients, and the outcome variable was CFDNA. Demographic variables included age, gender, tobacco consumption, and stage at diagnosis of cancer. Subjects with any known systemic disease, other tumors, or metastatic OSCC were excluded (CFDNA is altered in cases of tissue destruction and inflammatory diseases). The amount of CFDNA was determined through spectrophotometry (NanoDrop ND-1000 spectrophotometer; Thermo Fisher Scientific, Waltham, MA) in sampled blood and plasma. Mean and range for DNA quantification in plasma and blood were calculated in all groups and compared by use of the analysis of variance test. RESULTS A total of 390 cases (90 potentially malignant lesions, 150 OSCC cases, and 150 post-treatment OSCC cases) and 150 control subjects were studied. No significant difference was observed in levels of CFDNA in blood between the groups. Similarly, levels of CFDNA in plasma showed no significant difference except between the OSCC and potentially malignant groups, which was probably artifactual. CONCLUSIONS This study shows that disease progression in oral malignancy does not correlate with changes in levels of CFDNA in blood or plasma.

Association between GSTM1 and CYP1A1 polymorphisms and survival in oral cancer patients

AIMS Cancer patients inherited genotype may influence his or her survival, but evidence for the role of these genetic differences in oral cancer survival has not yet been explored. METHODS The authors evaluated polymorphisms in the GSTM1 and CYP1A1 genes for associations with overall survival in 100 oral squamous cell carcinoma (OSCC) treated patients and 100 controls who were followed up for survival within 2 years of the date of completion of their treatment. Overall survival was evaluated in Kaplan-Meier survival functions and Cox proportional hazards models. RESULTS After adjustment for stage and histology, GSTM1null genotype was associated with shorter survival among OSCC patients, compared with GSTM1 present genotype. There was no association between CYP1A1 C genotype and survival in the overall study population. CONCLUSION The study indicated a potential role for GSTM1 polymorphism in predicting the clinical outcomes of treated oral carcinoma patients.

Quantitative estimation of AgNORs in normal, dysplastic and malignant oral mucosa.

AIMS Silver stainable nucleolar organizer regions (AgNORs) have received a great deal of attention recently as their frequency within the nuclei is significantly higher in malignant cells than in normal, reactive or benign neoplastic cells. The objective of this study was to carry out a quantitative assessment of large and small AgNORs in oral normal mucosa, precancerous lesions and infiltrating squamous cell carcinomas. METHODS The study comprised 110 formalin-fixed, paraffin-embedded oral mucosal biopsies consisting of 30 oral dysplasia, 60 oral squamous cell carcinomas and 20 normal oral mucosa. AgNORs were counted in each nucleus, categorized as small, large and total number of AgNORs in each cell and their means were calculated. RESULTS The mean value of small AgNORs, large AgNORs and total AgNORs increased gradually from normal mucosa to dysplastic lesions to squamous cell carcinomas. The study clearly indicates that in oral squamous cell carcinomas, AgNORs diminish in size as they increase in number. Further, AgNOR counts increase as the degree of malignant potential of the cell increases. CONCLUSIONS By combining both the enumeration of AgNORs and their size, good distinction can be made between normal, dysplastic and infiltrating squamous cell carcinomas. This could help in the early diagnosis and prognosis of dysplastic mucosal lesions and their malignant transformation.

RETRACTED: Pink tooth phenomenon: An enigma?

BACKGROUND The appearance of pink teeth is a common phenomenon which has been observed after death in certain circumstances on post-mortem examination. Extra fibrinolytic activity of pulp facilitates rapid breakdown of red blood cells and diffusion of hemoglobin and its derivatives to flow into dentine. METHODS AND RESULTS We reviewed various studies on pink tooth phenomenon which have stated the various factors that lead to pink tooth formation. Most of the authors have stressed that post-mortem pink teeth must not be considered as a reliable odontological parameter for determining cause of death. CONCLUSION No correlation has been found between the occurrence of pink teeth and the cause of death but condition of the surroundings certainly plays an important role in the development of this phenomenon. This paper reviews the factors and conditions responsible for formation of pink teeth.

Craniometry and Malocclusion in Mentally Disabled Subjects in India

Background: The study aims to determine variations in craniofacial regions in mentally challenged individuals and to determine prevalence of malocclusion in these individuals. Methods: The malocclusion was identified and craniometric measurements were obtained among patients attending a special education program in Faculty of Dentistry, India. Results: The prevalence of malocclusion in the study population was 83%. Craniometric analysis revealed that brachycephalic, mesocephalic and hyperbracycephalic head shapes in different groups. Conclusion: In India, mentally disabled individuals have a higher prevalence of malocclusion than the general population and assessment of cranial characteristics of these persons may be of help to clinicians and researchers