Research over the years has generated enough evidence to implicate areca nut, as a carcinogen in humans. Besides oral, significant rise in the incidence of cancers of the oesophagus, liver and stomach was seen among areca nut chewers. Early diagnosis seems key to understand the initial processes of carcinogenesis which is highly curable. In North-East India, betel quid contains raw areca nut (RAN), lime and small portion of betel leaf without any other constituents. This study was not intended to isolate any active ingredients from the RAN and to look its action. The present objective is to validate the screening of precocious anaphase and analysis of expression of Securin and p53 in non-target cells like human peripheral blood lymphocytes (PBLs) and mouse bone marrow cells (BMCs) as early indicative parameters of RAN + lime-induced cancers. A total of 35 mice were examined at different time points for following ad libitum administration of RAN extract in drinking water with lime. Peripheral blood was collected from 32 human donors of which, 24 were RAN + lime heavy chewers. Expression of genes was assessed by immunoblotting and/or by immunohistochemistry. Histological preparation of stomach tissue of mice revealed that RAN + lime induced stomach cancer. A gradual increase in the frequency of precocious anaphases and aneuploid cells was observed in both RAN + lime-treated mouse BMC and human PBL of RAN heavy chewers. Levels of p53 and Securin were increased in these cells during early days of RAN + lime exposure. The level of Securin was significantly higher in human tumour samples than their adjacent normal counterpart. The expression of Securin was increased significantly in RAN + lime-administered mice as well as in stomach tumour. Present study revealed that precocious anaphase and expression of p53 and Securin in non-target cells are significantly associated with an increased risk of RAN-induced cancer and thus these parameters can be of early diagnostic value.

The Glutathione S-transferases (GSTs) protects cellular DNA against oxidative damage. The role of GSTP1 polymorphism (A313G; Ile105Val) as a susceptibility factor in oral cancer was evaluated in a hospital-based case-control study in NorthEast India, because the habit of chewing raw areca-nut (RAN) with/without tobacco is common in this region. Genetic polymorphism was investigated by genotyping 445 cases and 444 controls. Individuals with the GSTP1 AA-genotype showed association with the oral cancer (OR = 3.1, 95% CI = 2.4-4.2, p = 0.0002). Even after adjusting for age, sex and habit the AA-genotype is found to be significantly associated with oral cancer (OR = 2.4, 95% CI = 1.7-3.2, p = 0.0001). A protein-protein docking analysis demonstrated that in the GG-genotype the binding geometry between c-Jun Kinase and GSTP1 was disrupted. It was validated by immunohistochemistry in human samples, showing lower c-Jun-phosphorylation and down-regulation of pro-apoptotic genes in normal oral epithelial cells with the AA-genotype. In silico docking revealed that AA-genotype weakly detoxifies the RAN/tobacco metabolites. In addition, experiments revealed a higher level of 8-Oxo-2′deoxyguanosine induction in tumor samples with the AA-genotype. Thus, habit of using RAN/tobacco and GSTP1 AA-genotype together play a significant role in predisposition to oral cancer risk by showing higher DNA-lesions and lower c-Jun phosphorylation that may inhibit apoptosis. The oral squamous cell carcinoma (OSCC) is the most common cancer in India, with highest occurrence in the northeastern part of the country 1. The traditional habit of chewing raw rather than dry areca-nut with lime appears to be an important causative factor in addition of tobacco 2,3. In NorthEast India, particularly in Meghalaya, the betel-quid contains raw and unprocessed areca-nut (RAN), lime paste and small portion of betel-leaf but without tobacco. It has been noted that alkaloids, and polyphenols and tannic acid of RAN that are released in the saliva may contribute to carcinogenicity 4-6. It has been demonstrated that areca-nut alkaloids cause depression of antioxidants including glutathione and glutathione-S-transferases (GST) that are known to neutralize reactive oxygen species 7. Earlier studies indicate that RAN and lime together induce oral, esophagous and stomach cancers both in mouse and human and highlighted the occurrence of precocious anaphase (premature separation of sister-chromatids) and higher expression of p53 and Securin as a potential screening marker for identification of mitotic checkpoint defects during early days of RAN exposure 8,9. There are enough data to view lifestyle as well as genetic factors as important contributors for an individual's susceptibility to cancer 10. Glutathione redox and GST are supposed to play important roles in cellular

Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes.

Basal cell carcinoma is the most common form of skin cancer and it rarely metastasizes. The prevalence of metastatic basal cell carcinoma (MBCC) varies between 0.0028% and 0.55% of all cases. Over 250 MBCC have been reported in the literature. We present a case with large recurrent basal cell carcinoma of the face with radiological and histopathological findings indicating the presence of metastasis to the lungs.

Objective: To determine the incidence and risk factors associated with hearing loss in high risk neonates. Design: Descriptive cross sectional study. Setting: Level II NICU of a tertiary care hospital. Participants: 280 high risk infants were screened. Intervention: All high-risk babies were initially screened with both transient evoked otoacoustic emissions (TOAE) and Auditory brainstem response (ABR). Outcome variables: Primary: to determine the incidence of auditory neuropathy in high risk infants; Secondary: risk factors in those babies identified with hearing loss. Results: Incidence of hearing loss was 17.8 per 1000 screened (95% C.I is 0.24%-3.32%), with bilateral hearing loss seen in 14.2 per 1000 babies. Highest incidence of hearing loss was seen is in infants with intracranial haemorrhage and meningitis (50%) followed by in decreasing orders craniofacial anomalies (20%), intrauterine congenital infections (11.11%), culture positive sepsis including meningitis (8.88%), birth weight less than 1.5 kg (7.14%), preterm < 33 weeks (4.34%), severe birth asphyxia (4%), use of ototoxic medications for more than 5 days (3.03%). The risk of hearing loss is higher with higher number of risk factors. With a single risk factor being present, it is only 0.66%, whereas with five risk factors, the incidence was 33.3%. Conclusion: There is a high incidence of hearing loss in at-risk infants. Hearing loss is commoner when risk factors such as intracranial haemorrhage or meningitis are present and with presence of multiple risk factors. This would justify the need to routinely screen all high risk infants, so that rehabilitative measures can be initiated at the earliest.