OBJECTIVES: Mitochondrial dysfunction is a hallmark of cancer cells. Tobacco consumption in various forms is one of the major risk factors for the development of oral squamous cell carcinoma which makes the mitochondrial DNA susceptible to damage by reactive oxygen species. The GSTT1 and GSTM1 members of the glutathione S-transferase multigene family are candidate carcinogen metabolizing genes. Here we determined the hot spot mutations in the D-loop region and revealing correlation if any, with clinical parameters, along with analysing the genetic polymorphism of GSTT1 and GSTM1 and its susceptibility towards oral cancer. MATERIALS AND METHODS: To determine the hot spot mutations 25 matched tissue samples of OSCC patients with 25 control subjects were used for PCR and direct sequencing. Analysis for GSTM1 and GSTT1 gene polymorphism was done by multiplex PCR. RESULTS: Several mutations were found within the D-loop region among which mutations at nt146, nt152 and nt196 are found to be hot spot (P<0.0001, P<0.0001 and P<0.001 respectively). A significant association was found between the numbers of D-loop mutation and GSTM1 (OR=2.03; 95% CI, 1.04-3.96, P=0.003), GSTT1 (OR=1.73; 95% CI, 1.10-2.71, P=0.0027) null genotypes respectively. We observed a significant correlation between the increased number of D-loop mutations with the advancement in tumour stage of the patients (P=0.009, r=0.48). CONCLUSION: The association of null genotypes and mutations can be used as a possible biomarker for early detection and preventive measure of oral cancer for those habituated to tobacco consumption.
OBJECTIVES:Mitochondrial dysfunction is a hallmark of cancer cells. Tobacco consumption in various forms is one of the major risk factors for the development of oral squamous cell carcinoma which makes the mitochondrial DNA susceptible to damage by reactive oxygen species. The GSTT1 and GSTM1 members of the glutathione S-transferase multigene family are candidate carcinogen metabolizing genes. Here we determined the hot spot mutations in the D-loop region and revealing correlation if any, with clinical parameters, along with analysing the genetic polymorphism of GSTT1 and GSTM1 and its susceptibility towards oral cancer. MATERIALS AND METHODS: To determine the hot spot mutations 25 matched tissue samples of OSCC patients with 25 control subjects were used for PCR and direct sequencing. Analysis for GSTM1 and GSTT1 gene polymorphism was done by multiplex PCR. RESULTS: Several mutations were found within the D-loop region among which mutations at nt146, nt152 and nt196 are found to be hot spot (P<0.0001, P<0.0001 and P<0.001 respectively). A significant association was found between the numbers of D-loop mutation and GSTM1 (OR=2.03; 95% CI, 1.04-3.96, P=0.003), GSTT1 (OR=1.73; 95% CI, 1.10-2.71, P=0.0027) null genotypes respectively. We observed a significant correlation between the increased number of D-loop mutations with the advancement in tumour stage of the patients (P=0.009, r=0.48). CONCLUSION: The association of null genotypes and mutations can be used as a possible biomarker for early detection and preventive measure of oral cancer for those habituated to tobacco consumption.
Authors: Adrian D Schubert; Esther Channah Broner; Nishant Agrawal; Nyall London; Alexander Pearson; Anuj Gupta; Neha Wali; Tanguy Y Seiwert; Sarah Wheelan; Mark Lingen; Kay Macleod; Hailey Allen; Aditi Chatterjee; Saloura Vassiliki; Daria Gaykalova; Mohammad O Hoque; David Sidransky; Karthik Suresh; Evgeny Izumchenko Journal: Cancer Lett Date: 2019-12-10 Impact factor: 8.679