Journal of Cancer Research and Therapeutics

REVIEW ARTICLE
Year
: 2013  |  Volume : 9  |  Issue : 2  |  Page : 179--180

Molecular biology of oral sub mucous fibrosis


K Saravanan1, M Kodanda Ram2, R Ganesh3,  
1 Department of Oral and Maxillofacial Surgery,Vinayaka Mission's Sankarachariyar Dental College and Hospital, Vinayaka Missions Deemed University, Sankari Main Road, Ariyanoor, Salem, India
2 Department of Oral Pathology, Kannur Dental College, Kannur university, Kerala, India
3 Department of Pedodontics, SRM Dental College, SRM deemed university, Ramapuram, Chennai, India

Correspondence Address:
K Saravanan
Department of Oral and Maxillofacial Surgery, Vinayaka Mission«SQ»s Sankarachariyar Dental College and Hospital, Sankari Main Road, Ariyanoor, Salem
India

Abstract

Oral sub mucous fibrosis is an insidious chronic disease affecting any part of the oral cavity. Worldwide estimates of oral sub mucous fibrosis indicate that 2.5 million people are affected, with most cases concentrated in the Indian subcontinent, especially eastern and southern India. Oral sub mucous fibrosis has a propensity for malignant transformation. The association of betel quid chewing, oral sub mucous fibrosis, and oral squamous cell carcinoma is quite profound, especially in Taiwan and the Indian subcontinent where up to 80% of oral squamous cell carcinoma is associated with the habit. Epidemiological studies have shown that the rate of malignant transformation ranges from 3 to 19%.



How to cite this article:
Saravanan K, Ram M K, Ganesh R. Molecular biology of oral sub mucous fibrosis.J Can Res Ther 2013;9:179-180


How to cite this URL:
Saravanan K, Ram M K, Ganesh R. Molecular biology of oral sub mucous fibrosis. J Can Res Ther [serial online] 2013 [cited 2019 Oct 20 ];9:179-180
Available from: http://www.cancerjournal.net/text.asp?2013/9/2/179/113340


Full Text

 Introduction



In 1952, Schwartz coined the term "atrophic­aidiopathica mucosa oris" to describe an "oral fibrosing" disease that he discovered in five Indian women from Kenya. [1] Joshi subsequently termed the condition oral sub mucous fibrosis (OSF) in 1953. [2] Pindborg in 1966 defined OSF as an insidious chronic disease affecting any part of the oral cavity and sometimes pharynx, al though occasionally preceded by and\or associated with vesicle formation, it is always associated with juxtaepithelial inflammatory reaction followed by fibroelastic changes in the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa causing trismus and difficulty in eating. [3]

OSF has a propensity for malignant transformation. The association of betel quid chewing, OSF, and oral squamous cell carcinoma is quite profound, especially in Taiwan and the Indian subcontinent where up to 80% of oral squamous cell carcinoma is associated with the habit. Epidemiological studies have shown that the rate of malignant transformation ranges from 3 to 19%. [4]

One of the early genetic studies found a statistically significant increase in the size C-band heteromorphism patterns on chromosome1 in OSF and oral squamous cell carcinoma patients when compared with healthy subjects. OSF lesions abnormally express and stain positive for p53, a specific clustered mutation in exon 5 of the p53 gene. Expression levels and mutation frequencies of p53 are progressively higher in oral squamous cell carcinoma than in sub mucous fibrosis lesions. Another tumor suppressor gene, adenomatous polyposis coli (APC), could also potentially be involved in the malignant potential of OSF. [5],[6]

The most important DNA lesions produced by both carcinogens and chemotherapeutic alkylating agents such as tobacco-specific nitrosamines (TSNAs), nitrosoureas, and related compounds are O 6 -alkyl guanine adducts. [7] The ability of these adducts to pair with thymine instead of cytosine during DNA replication is responsible for the increase in frequency of transition mutations. O 6 -methyl guanine DNA methyltransferase (MGMT) is a DNA repair enzyme involved in protection of the cellular genome from mutagenic actions of endogenous and environmental carcinogens. Abnormal MGMT expression causes O 6 -methyl guanine to accumulate in cellular DNA, and this could result in activation of oncogenes or inactivation of tumor suppressor genes, contributing to carcinogenesis or tumor progression. [7]

Collagen-related genes play an important role in the homeostasis of collagen metabolism. There is evidence to suggest that collagen-related genes are altered due to ingredients in the quid. The genes COL1A2, COL3A1, COL6A1, COL6A3, and COL7A1 have been identified as definite transforming growth factor (TGF)-beta targets and are induced in fibroblasts at early stages of the disease. The transcriptional activation of procollagen genes by TGF-beta suggests that it may contribute to increased collagen levels of OSF. [8]

Few studies have shown that human leukocyte antigen (HLA) typing in OSF patients. Polym erase chain reaction (PCR) has shown a significant increase in the frequencies of HLA-A24, DRB1-11, and DRB3-0202/3. The association of HLA and OSF does not appear consistently as there is no demonstrable specific pattern of HLA antigen frequencies in chewers with or without the disease. Although the data on various HLA types, increased autoantibodies, and the detection of immune complexes tend to indicate an autoimmune basis for the disease, substantial number of cases and matched controls may be required to verify these findings. [9]

It is possible to use premalignant and malignant cells for analyzing the DNA patterns and ploidy in cytophotometry. [10] The presence of a large genetically altered event such as DNA ploidy is a risk factor for the development of head and neck squamous cell carcinomas. Therefore, the analysis of genetically altered mucosa might identify the subgroup of patients at high risk for developing squamous cell carcinoma. Other parameters should be taken into account as well, such as follow-up, time, and certain specific genetic alterations. If such a high-risk patient group can be identified, chemoprevention or gene therapy is thepotential therapeutic approach to prevent the development of head and neck squamous cell carcinomas.

The DNA ploidy is a significant prognostic marker in patients with premalignant lesion. [11] Since squamous cell carcinoma develops in relatively a few patients with hyperplasia, it is likely that subtle genetic factors also influence the malignant transformation of oral white patches. The identification of patients who are particularly in need of preventive counseling or active treatment remains a challenge to the clinician. Whether intensified treatment of aneuploid in dysplasias will reduce the incidence and rate of death from squamous cell carcinomas is unknown.

The DNA content that is represented as DNA ploidy of a cell gives a direct measurement of the genetic instability and DNA aberration. It is revealed that in premalignant patients, genetically stable diploid cells were replaced by genetically unstable tetraploid cells. In malignant patients with squamous cell carcinoma, in addition to the presence of genetically unstable tetraploid cells, genetically unstable triploid cells are detected.

The DNA aneuploidy has a powerful predictor value during the subsequent development of premalignant dysplasia associated with or without a malignancy, whereas normal DNA content indicates a low risk.

 Conclusion



Furtherresearch is required in order to identify the mech­anismleading to carcinogenesis in this type of fibrotic oral mucosa. Nutritional deficiencies may not play a primary role but it could synergize the symptomotology bycontributing to epithelial atrophy. Although theinvolvement of HLA and genetic predisposition has been reported, specific haplotypes have not beendetermined. The individual mechanisms operating atvarious stages of the disease-initial, intermediate and advanced-need further study in order to proposeappropriate therapeutic interventions. The present findings are promising to supplement clinical and histopathological parameters in evaluating prognosis and to demonstrate methods that are readily applicable for routine diagnostic work.

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