title: Mitochondrial DNA copy number and risk of oral cancer: a report from Northeast India.
abstract: BACKGROUND
  Oral 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Biotechnology, Assam University, Silchar, Assam, India.
authors.forename: Rosy
authors.initials: R
authors.lastname: Mondal
authors.forename: Sankar Kumar
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Javed Hussain
authors.initials: JH
authors.lastname: Choudhury
authors.forename: Anil
authors.initials: A
authors.lastname: Seram
authors.forename: Kavita
authors.initials: K
authors.lastname: Sinha
authors.forename: Marine
authors.initials: M
authors.lastname: Hussain
authors.forename: Ruhina Shirin
authors.initials: RS
authors.lastname: Laskar
authors.forename: Bijuli
authors.initials: B
authors.lastname: Rabha
authors.forename: Pradip
authors.initials: P
authors.lastname: Dey
authors.forename: Sabitri
authors.initials: S
authors.lastname: Ganguli
authors.forename: Monisha
authors.initials: M
authors.lastname: Nathchoudhury
authors.forename: Fazlur Rahman
authors.initials: FR
authors.lastname: Talukdar
authors.forename: Biswadeep
authors.initials: B
authors.lastname: Chaudhuri
authors.forename: Bishal
authors.initials: B
authors.lastname: Dhar
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000172:deficiency* / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000472:pathogenicity; D052161:Human papillomavirus 18 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D012306:Risk; D014030:Tobacco, Smokeless / Q000009:adverse effects
chemical_list: D004272:DNA, Mitochondrial; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1