BackgroundOral squamous cell carcinoma (OSCC) is the sixth most common cancer globally. Tobacco consumption and HPV infection, both are the major risk factor for the development of oral cancer and causes mitochondrial dysfunction. Genetic polymorphisms in xenobiotic-metabolizing enzymes modify the effect of environmental exposures, thereby playing a significant role in gene–environment interactions and hence contributing to the individual susceptibility to cancer. Here, we have investigated the association of tobacco - betel quid chewing, HPV infection, GSTM1-GSTT1 null genotypes, and tumour stages with mitochondrial DNA (mtDNA) content variation in oral cancer patients.Methodology/Principal FindingsThe study comprised of 124 cases of OSCC and 140 control subjects to PCR based detection was done for high-risk HPV using a consensus primer and multiplex PCR was done for detection of GSTM1-GSTT1 polymorphism. A comparative ΔCt method was used for determination of mtDNA content. The risk of OSCC increased with the ceased mtDNA copy number (Ptrend = 0.003). The association between mtDNA copy number and OSCC risk was evident among tobacco – betel quid chewers rather than tobacco – betel quid non chewers; the interaction between mtDNA copy number and tobacco – betel quid was significant (P = 0.0005). Significant difference was observed between GSTM1 - GSTT1 null genotypes (P = 0.04, P = 0.001 respectively) and HPV infection (P<0.001) with mtDNA content variation in cases and controls. Positive correlation was found with decrease in mtDNA content with the increase in tumour stages (P<0.001). We are reporting for the first time the association of HPV infection and GSTM1-GSTT1 null genotypes with mtDNA content in OSCC.ConclusionOur results indicate that the mtDNA content in tumour tissues changes with tumour stage and tobacco-betel quid chewing habits while low levels of mtDNA content suggests invasive thereby serving as a biomarker in detection of OSCC.

BackgroundEpigenetic and genetic alteration plays a major role to the development of head and neck squamous cell carcinoma (HNSCC). Consumption of tobacco (smoking/chewing) and human papilloma virus (HPV) are also associated with an increase the risk of HNSCC. Promoter hypermethylation of the tumor suppression genes is related with transcriptional inactivation and loss of gene expression. We investigated epigenetic alteration (promoter methylation of tumor-related genes/loci) in tumor tissues in the context of genetic alteration, viral infection, and tobacco exposure and survival status.MethodologyThe study included 116 tissue samples (71 tumor and 45 normal tissues) from the Northeast Indian population. Methylation specific polymerase chain reaction (MSP) was used to determine the methylation status of 10 tumor-related genes/loci (p16, DAPK, RASSF1, BRAC1, GSTP1, ECAD, MLH1, MINT1, MINT2 and MINT31). Polymorphisms of CYP1A1, GST (M1 & T1), XRCC1and XRCC2 genes were studied by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex-PCR respectively.Principal FindingsUnsupervised hierarchical clustering analysis based on methylation pattern had identified two tumor clusters, which significantly differ by CpG island methylator phenotype (CIMP), tobacco, GSTM1, CYP1A1, HPV and survival status. Analyzing methylation of genes/loci individually, we have found significant higher methylation of DAPK, RASSF1, p16 and MINT31genes (P = 0.031, 0.013, 0.031 and 0.015 respectively) in HPV (+) cases compared to HPV (-). Furthermore, a CIMP-high and Cluster-1 characteristic was also associated with poor survival.ConclusionsPromoter methylation profiles reflecting a correlation with tobacco, HPV, survival status and genetic alteration and may act as a marker to determine subtypes and patient outcome in HNSCC.

The stretching and bending vibrational energies of SnBr4 and CCl4 are calculated in the one-dimensional framework. The dynamical symmetry group of tetrahedral molecule was taken into consideration to construct the model Hamiltonian in this framework. Casimir and Majorana invariant operators were also determined accordingly. Using the model Hamiltonian so constructed, we reported the vibrational energy levels of SnBr4 and CCl4 molecules accurately.

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Tobacco consumption in various forms is one of the major risk factor for the development of head and neck squamous cell carcinoma. Polymorphisms in XRCC1 and XRCC2 genes may alter an individual's susceptibility to tobacco-related cancers. Here, we have investigated the interaction of XRCC1 (Arg399Gln) and XRCC2 (Arg188His) polymorphism and tobacco exposure in the progression of HNSCC in northeast Indian population. The population-based case-control study includes 110 HNSCC patients and 140 controls. The polymorphisms of XRCC1 and XRCC2 were studied by means of PCR-RFLP, and the results were confirmed by DNA sequencing. Smokers and tobacco-betel quid chewers were significantly higher in cases (P = 0.045 and 0.033). The variant homozygote AA genotype of XRCC1 Arg399Gln and heterozygote GA genotype of XRCC2 Arg188His has an increased risk toward HNSCC (OR 2.43; P = 0.031 and OR 3.29; P < 0.01, respectively). The interaction between tobacco-betel quid chewing and variant genotypes of XRCC1 and XRCC2 resulted in several fold increase the risk of HNSCC, when compared to non-chewers. Heavy smokers carrying XRCC1 AA and XRCC2 GA genotypes had a significantly higher risk of HNSCC compared to never smokers (P = 0.017 and 0.003, respectively). Upon gene-gene interaction analysis, individuals carrying both XRCC1 GA (Arg/Gln) and XRCC2 GA (Arg/His) genotypes had the highest risk of HNSCC (P = 0.001).Our finding suggests that interaction of tobacco and polymorphisms of XRCC1 and XRCC2 increases the risk of HNSCC. Furthermore, cross talk between these two DNA repair genes might modulate susceptibility toward HNSCC.