Genetic variations of TLRs and their association with HPV/EBV, co-infection along with nicotine exposure in the development of premalignant/malignant lesions of the oral cavity in Indian population

• Published in: Cancer epidemiology Vol. 61; pp. 38 - 49
• Main Authors: Sharma, Upma, Singhal, Pallavi, Bandil, Kapil, Patle, Rajeshwar, kumar, Anoop, Neyaz, Kausar, Bose, Surojit, Kumar Dewan, Ajay, Mehrotra, Ravi, Sharma, Veena, Bharadwaj, Mausumi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2019; Elsevier Limited
• Subjects: Adult; Alcohol; Antigen-presenting cells (APCs); Asian Continental Ancestry Group; Carcinoma, Squamous Cell - epidemiology; Chewing; Coinfection - genetics; Deoxyribonucleic acid; DNA; Epidemiology; Epstein Bar virus (EBV); Epstein-Barr Virus Infections - genetics; Female; Gene polymorphism; Genetic diversity; Genetic Variation; Herpesvirus 4, Human - genetics; Human papillomavirus; Human papillomavirus (HPV); Humans; India - epidemiology; Infections; Leukokeratosis; Lifestyles; Male; Malignancy; Microorganisms; Middle Aged; Mouth Neoplasms - etiology; Mouth Neoplasms - genetics; Nicotine; Nicotine - adverse effects; Oral cancer; Oral cancer (OC); Oral cavity; Oral squamous cell carcinoma (OSCC); Oral submucous fibrosis (OSMF); Papillomavirus Infections - virology; Polymorphism, Genetic - genetics; Population studies; Risk factors; Single nucleotide polymorphisms (SNPs); Smoking; Squamous cell carcinoma; Statistical analysis; Tobacco; Tobacco, Smokeless - adverse effects; Toll-like receptors (TLRs); Viral infections; India; Toll-like receptors (TLRs); Oral squamous cell carcinoma (OSCC); Epstein Bar virus (EBV); Single nucleotide polymorphisms (SNPs); Oral cancer (OC); Oral submucous fibrosis (OSMF); Human papillomavirus (HPV); Antigen-presenting cells (APCs)
• ISSN: 1877-7821; 1877-783X; 1877-783X
• DOI: 10.1016/j.canep.2019.05.003

•The frequency of single infection (HPV+/EBV-) was higher in cancer and co-infection (HPV++EBV+) was in pre-cancer.•The association between TLR 9(-1486T/C) and HPV/EBV, co-infection may play an important role in initiation of the disease.•TLR 9(-1486T/C) polymorphism and its association with lifestyle habits may also increase the risk of premalignant lesions.•TLR 4 (+896A/G) showed a higher risk of developing oral pre-cancerous lesions in smokers and tobacco chewers. 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.