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Key words: p53 polymorphism; HPV; oral cancerOral squamous cell carcinoma (OSCC) is the sixth most common malignancy and is a major cause of cancer morbidity and mortality worldwide. The overall survival percentage has not changed in recent years, despite extensive research on the biological and molecular aspects of oral SCC. Among the more pressing problems in clinical management are the lack of early detection and the high incidence of local-regional recurrence, even with aggressive surgical therapy. OSCC incidence accounts for up to 40% of all malignancies in India and South East Asia. 1 Moreover differences have been observed in the clinico-pathological and molecular pathological profile in the tobacco smoking and alcoholassociated oral cancers in the USA, UK, France, Japan, etc. and the chewing tobacco-associated oral cancers, particularly in the Indian sub-continent. 2 In India, oral leukoplakias have been reported to show a significant tendency to malignant transformation from 0.13 to 6% and rising to 14% or higher in cases of dysplasia. 3,4 Epidemiological studies reveal the betel quid and tobacco chewing habit as an important risk factor in the etiology of oral cancer in India. Since carcinogenesis is a multi-step process, therefore, in addition to insult by tobacco-associated intra oral carcinogens, several additional factors, such as genetic susceptibility of individuals and external agents, such as dietary factors and viruses (human papillomavirus, HPV, and Epstein-Baar virus, EBV), may play a synergetic role in oral tumorigenesis. [5][6][7][8] HPVs are a very heterogenous group of DNA viruses. Almost 90 HPV types have been described; 30 of these types are associated with anogenital cancers, forming either the high-risk types (HPV16 and HPV18) that are associated with anogenital invasive tumour and their precursor lesions or the low-risk types (HPV6 and HPV11) that rarely progress to malignancy. Analysis of viral genome has revealed that 2 early genes, E6 and E7, of high risk HPVs (16/18) are transforming genes that are responsible for maintenance of tumorigenic phenotype. 6,9,10 Genetic polymorphism at the genes involved in tumorigenesis may determine individual susceptibility of cancer. The genotype distribution of p53 codon 72 polymorphism is significantly different among ethnic groups. 11 Storey et al. 12 recently reported the probable correlation between p53 polymorphism and HPV associated cervical tumorigenesis. They showed that population homozygous for Arg-72 (arginine) is about 7 times more susceptible to development of cervical cancer than heterozygotes. However, this has been subject of much debate. Makni et al. 13 recently showed the substantial inter-laboratory variation in the proportion of Arg/Arg, Arg/Pro (proline) and Pro/Pro.In spite of its great relevance, so far only 2 contradictory reports have been proposed on the status of HPV in oral cancer on Indian population. The work on South Indian population has indicated 42% HPV-16 infection and 47% of HPV-18 infection, 7 whereas the r...

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BACKGROUND:The VDR protein is at the centre of the vitamin D endocrine system, a complex physiological system with substantial feedback regulatory mechanisms involved in maintaining serum calcium and 1, 25 dihydroxy vitamin D3. Variations in VDR gene are shown to have implications in several diseases and have also been implicated as an important genetic factor affecting bone mass.AIM:To determine the frequency of Fok I and Taq I variants in healthy Indian individuals and its association with 25-OH-Vitamin D levels.SETTINGS AND DESIGN:Blood samples were collected from 143 unrelated normal individuals (Male-84 and Female-59) and their genotypes determined.MATERIALS AND METHODS:After amplification by polymerase chain reaction, each polymorphism was genotyped by restriction fragment length polymorphism. For 100 normal healthy individuals 25-hydroxyvitamin D estimation was done using DiaSorin kit method.STATISTICAL ANALYSIS:Graph pad software was used to calculate the P values from the Chi-square.RESULTS:Out of 143 samples analyzed for FokI and TaqI polymorphisms the following genotypic frequency was obtained FF 59%, Ff 36%, ff 5% and TT 49%, Tt 43%, tt 8% respectively.CONCLUSIONS:Results indicate that the distribution of the polymorphic loci Fok I and Taq I vary considerably not only in different populations, but also within India. Furthermore, when the genotypes were analyzed with respect to 25-OH-Vitamin D levels, a significant association was seen for the Taq 1 SNP but not with the Fok I.

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Epidemiological evidence suggests that heavy consumption of betel quid and tobacco with areca nuts is the cause of high incidence of oral cancer in eastern part of Indian population, which is distinctly different from the etiology of oral squamous cell carcinomas (SCCs) in western countries. Here, expression of p53 and c-myc protein was studied in oral SCCs from this etiologically distinct population by immunohistochemistry. Out of 48 specimens of oral SCCs, 22 (45.8%) exhibited p53 positivity and 27 (56.3%) showed immunoreactivity with c-myc antibody. Considering the p53/c-myc expression pattern, either alone or in combination, the population was divided into four groups, i.e., both p53 and c-myc positive; p53 positive-c-myc negative; c-myc positive - p53 negative; and both p53 and c-myc negative. Tumours with both p53 and c-myc positivity were in advanced stages of the disease (poorly differentiated, tumour stage 3, nuclear grade III), whereas earliest stage of oral SCCs was detected in tumours with neither p53 nor c-myc immunoreactivity. Tumours of remaining two groups were generally restricted to early to moderate stages. These observations suggest that rapid progression of the betel- and tobacco-related oral SCCs may be associated with a simultaneous involvement of these two oncoproteins. The study also attempted to find out the relationship of p53/c-myc expression with spontaneous apoptosis. More apoptotic cells were found in c-myc positive but p53 negative tumours. This preliminary observation requires further molecular investigation of the role of p53 and c-myc genes for the progression of this epidemiologically distinct oral carcinogenesis.

Stat-3 activation is an early event in head and neck carcinogenesis though its role in blocking the apoptosis in vivo in solid tumors was not observed.

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