Abstract
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.
Highlights
Oral squamous cell carcinoma (OSCC), the most frequent tumour of oral cavity, [1] and the sixth most common cancer globally that accounts for approximately 5 per cent of all malignant tumours worldwide [2,3]
Our results indicate that the mitochondrial DNA (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
The increase risk to OSCC is 2.2- fold among the tobacco-betel quid chewers which is one of the major contributing factors for oral cancer and in Northeast India tobacco chewing is one of the customary practices
Summary
OSCC, the most frequent tumour of oral cavity, [1] and the sixth most common cancer globally that accounts for approximately 5 per cent of all malignant tumours worldwide [2,3]. Smokeless tobacco products and betel quid with or without tobacco are the major risk factors for oral cavity cancer in Taiwan, India, and other neighboring countries [5,6,7]. Alcohol use, smokeless tobacco products, and HPV (Human papilloma virus) infections are the major risk factors for oral cavity cancer, with smoking and alcohol having synergistic effects [9,10]. Tobacco consumption and HPV infection, both are the major risk factor for the development of oral cancer and causes mitochondrial dysfunction. 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
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