Upma Sharma1, Pallavi Singhal2, Kapil Bandil2, Rajeshwar Patle2, Anoop Kumar3, Kausar Neyaz4, Surojit Bose5, Ajay Kumar Dewan6, Ravi Mehrotra7, Veena Sharma8, Mausumi Bharadwaj9. 1. Division of Molecular Genetics & Biochemistry, Division of Cytopathology, National Institute of Cancer Prevention & Research (ICMR-NICPR), I-7, Sector-39, Noida, India; Department of Bioscience and Biotechnology, Banasthali University, Rajasthan, India. 2. Division of Molecular Genetics & Biochemistry, Division of Cytopathology, National Institute of Cancer Prevention & Research (ICMR-NICPR), I-7, Sector-39, Noida, India. 3. Division of Molecular Genetics & Biochemistry, Division of Cytopathology, National Institute of Cancer Prevention & Research (ICMR-NICPR), I-7, Sector-39, Noida, India; National Institute of Biologicals, Noida, Uttar Pradesh, India. 4. Human Diagnostics R & D, DSS Imagetech Private Limited, New Delhi, India. 5. Awadh Dental College and Hospital, Kolkata, India. 6. Department of Surgical Oncology & Department of Research, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi, India. 7. Division of Cytopathology, National Institute of Cancer Prevention & Research (ICMR-NICPR), I-7, Sector-39, Noida, India. 8. Department of Bioscience and Biotechnology, Banasthali University, Rajasthan, India. 9. Division of Molecular Genetics & Biochemistry, Division of Cytopathology, National Institute of Cancer Prevention & Research (ICMR-NICPR), I-7, Sector-39, Noida, India. Electronic address: bharadwajm@icmr.org.in.
Abstract
BACKGROUND: Despite being most preventable malignancies associated with smoked and smokeless tobacco products, squamous cell carcinoma of oral cavity is one of the most common malignancy in India. The aim of the present study was to evaluate the role of TLRs in oral pre-cancerous, cancerous cases and their genotypic correlation with HPV/EBV, co-infection & lifestyle habits in Indian population. METHODS: The present study was conducted on 300 subjects (100 OSCC, 50 pre-cancer & 150 controls). The amplification of TLRs gene and HPV/EBV co-infection was assessed by Nested PCR, PCR-RFLP and further confirmation by direct sequencing. RESULTS: The TLR 9(-1486 T/C), revealed that the TT vs. CT + CC genotype had a ˜5-fold increased risk for the development of pre-cancerous lesions as compared to controls (p = 0.0001). Further analysis showed that the risk of cancer was extremely pronounced in HPV/EBV, co-infection (p = 0.0141), implicating the possible interaction between TLR 9(-1486T/C) genotype and HPV infection in increasing cancer/pre-cancer risk. The 'G' allele of TLR 4(+896A/G) was also a higher risk of developing pre-cancerous lesions with 4.5 fold and statistically significant (p = 0.0001). The genotypic association of TLR 9(-1486T/C) in OSMF cases showed ˜8 fold increased risk and TLR 4(+896A/G) showed fourteen fold higher risk for leukoplakia (p < 0.0001, OR = 14.000). CONCLUSION: Genetic polymorphism of TLR 9(-1486 T/C) and TLR 4(+896A/G) may influence the effects of HPV/EBV, co-infection and play the significant role in development of the disease. The significance of these TLRs seemed to be enhanced by tobacco chewing and smoking habits also, which act as an important etiological risk factor for OSCC.
BACKGROUND: Despite being most preventable malignancies associated with smoked and smokeless tobacco products, squamous cell carcinoma of oral cavity is one of the most common malignancy in India. The aim of the present study was to evaluate the role of TLRs in oral pre-cancerous, cancerous cases and their genotypic correlation with HPV/EBV, co-infection & lifestyle habits in Indian population. METHODS: The present study was conducted on 300 subjects (100 OSCC, 50 pre-cancer & 150 controls). The amplification of TLRs gene and HPV/EBV co-infection was assessed by Nested PCR, PCR-RFLP and further confirmation by direct sequencing. RESULTS: The TLR 9(-1486 T/C), revealed that the TT vs. CT + CC genotype had a ˜5-fold increased risk for the development of pre-cancerous lesions as compared to controls (p = 0.0001). Further analysis showed that the risk of cancer was extremely pronounced in HPV/EBV, co-infection (p = 0.0141), implicating the possible interaction between TLR 9(-1486T/C) genotype and HPV infection in increasing cancer/pre-cancer risk. The 'G' allele of TLR 4(+896A/G) was also a higher risk of developing pre-cancerous lesions with 4.5 fold and statistically significant (p = 0.0001). The genotypic association of TLR 9(-1486T/C) in OSMF cases showed ˜8 fold increased risk and TLR 4(+896A/G) showed fourteen fold higher risk for leukoplakia (p < 0.0001, OR = 14.000). CONCLUSION: Genetic polymorphism of TLR 9(-1486 T/C) and TLR 4(+896A/G) may influence the effects of HPV/EBV, co-infection and play the significant role in development of the disease. The significance of these TLRs seemed to be enhanced by tobacco chewing and smoking habits also, which act as an important etiological risk factor for OSCC.
Authors: Shivaranjhany Sivakumar; Archana A Gupta; Nik Mohd Mazuan Nik Mohd Rosdy; Annapurny Venkiteswaran; A Thirumal Raj; Kamran Habib Awan Journal: Transl Cancer Res Date: 2020-04 Impact factor: 1.241