ReviewOral cancer: reviewing the present understanding of its molecular mechanism and exploring the future directions for its effective management
Introduction
Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. Globally about 500,000 new oral and pharyngeal cancers are diagnosed annually, and three quarters of these are from the developing world [1]. Oral cancer is an epithelial neoplasia generally beginning as a focal clonal overgrowth of altered stem cells near the basement membrane, expanding upward and laterally, replacing the normal epithelium. The neoplastic process is a beginning with normal epithelium progressing through hyperplasia to dysplasia to carcinoma in situ and invasive carcinoma [2]. Oral carcinogenesis is associated with cumulative gene alterations. In neoplasms, cell proliferation is excessive and autonomous, uncoordinated with normal tissues with cell division going on despite DNA damage due to loss of cell cycle check-points. These neoplastic cells ultimately enters lymphatic vessels and metastasize to regional lymph nodes. Age standardized incidence rate of head and neck cancer in males exceeds 30/100,000 in regions of France, Hong Kong, the Indian sub-continent, Central/Eastern/Southern Europe, regions of South America, and among US blacks. High rates (>10/100,000) in females are found in India and Hong Kong [3]. Oral cancers are common in regions with high tobacco and alcohol consumption. In south-east Asian countries people extensively use smokeless tobacco in the form of nass, naswar, khaini, pan masala, gutkha and betel quid (betel leaf coated with slaked line wrapped around areca nut and catechu) or tobacco smoking in the form of cigarette, bidi, chutta, reverse type of smoking and hooka. Hence, in this part of world Buccal Mucosa (cheek) represents the primary site for cancer development as compared with tongue and floor of mouth in Western Countries [4]. Since, carcinogenesis is a multi-step process hence in addition to genetic insult by tobacco-associated intra-oral carcinogens, several additional factors, such as genetic susceptibility of individuals and external agents, such as alcohol, dietary factors and viruses (human papilloma virus, HPV, and Epstein–Barr virus, EBV), may play a synergetic role in oral tumorigenesis [5].
Oral cancer is one of the few cancer types where it is possible to obtain biopsies at all stages of cancer progression. Consequently, it is possible to define a genetic progression model of this disease. The pioneer work characterizing the genetic alterations in colorectal cancer by Fearon and Vogelstein [6] has become a paradigm for other human neoplasias. It is now believed that OSCC follows a similar pattern in its development, and thus is preceeded by premalignant lesions such as leukoplakia, dysplasia, erythroplakia, lichen planus and oral sub-mucous fibrosis (OSMF). The precise nature of the genetic alterations occurring at each step is still unclear, but Califano et al. [7] have described a preliminary HNSCC molecular progression model. Five years survival rates for mouth, tongue, oropharynx and laryngopharyngeal cancers seldom exceed 40%. Involvement of regional lymph nodes is the most important prognostic factor for oral cancer.
Section snippets
Molecular alterations in oral cancer
Cancer evolves in a series of distinct steps, each characterized by the sequential accumulation of additional genetic defects followed by clonal expansion.
Switching to new technologies for systematic identification and cataloguing of genes involved in oral carcinogenesis
The emphasis in oncology during the past decade has been on the incorporation of genomics tool into oncological research and now, in the post genomic era, there is a strong drive to incorporate proteomics technologies into oncology research. With the human genome being sequenced many biotech companies are venturing in the field of Operomics, with the goal of applying this knowledge for anti-cancer drug discovery and molecular diagnosis of cancer. Operomics, an approach that integrates genomics,
Acknowledgements
This work was supported in the form of Research Grants to Professor B.R. Das from Department of Biotechnology (BT/R&D/091/066/96 and BT/PR1347/HRD/15/131/98), Govt. of India; Council of Scientific and Industrial Research, Government of India. The financial support from the Department of Biotechnology, New Delhi and Council of Scientific and Industrial Research, New Delhi to BRD is highly acknowledged. JKN thanks the Council of Scientific and Industrial Research, New Delhi, for a research
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2016, Archives of Oral BiologyCitation Excerpt :These chromosomal aberrations consistently influence the expression and function of some very important tumor regulating genes such as p16 (9p21), APC (5q21-22) and p53 (17p13). Genetic polymorphisms in glutathione S-transferase M1 (GSTM1), the cytochrome P450 family 1 member A1 (CYP1A1), and aldehyde dehydrogenase (ALDH1B & ALDH2) are found to be strongly and specifically correlated with the risk of OSCC (Jefferies et al.,1999; Tripathy & Roy, 2006; Brennan et al., 2004; Ram et al., 2011; Reis et al., 2002; Sartor et al., 1999; Taylor et al., 1999; Nagpal & Das, 2003). Epigenetic modifications such as the methylation of DNA and acetylation or methylation of histones also play a key role in silencing of tumor suppressor genes in OSCC (Feller et al., 2010a).