- Volume 17 Issue 7
DOI QR Code
Roles of CYP1A1 and CYP2E1 Gene Polymorphisms in Oral Submucous Fibrosis
- Yaming, Punyo (Department of Oral Pathology and Microbiology, Maulana Azad Institute of Dental Sciences) ;
- Urs, Aadithya Basavaraj (Department of Oral Pathology and Microbiology, Maulana Azad Institute of Dental Sciences) ;
- Saxena, Alpana (Department of Biochemistry, Maulana Azad Medical College) ;
- Zuberi, Mariyam (Department of Biochemistry, Maulana Azad Medical College)
- Published : 2016.07.01
Background: Oral submucous fibrosis (OSF) is a precancerous condition with a 4 to13% malignant transformation rate. Related to the habit of areca nut chewing it is mainly prevalent in South-east Asian countries where the habit of betel quid chewing is frequently practised. On chewing, alkaloids and polyphenols are released which undergo nitrosation and give rise to N-nitrosamines which are cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various endogenous and exogenous chemicals including those released by areca nut chewing. CYP1A1 plays a central role in metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes nitrosamines and tannins. Polymorphisms in genes that code for these enzymes may alter their expression or function and may therefore affect an individuals susceptibility regarding OSF and oral cancer. The present study was therefore undertaken to investigate the association of polymorphisms in CYP1A1 m2 and CYP2E1 (RsaI/PstI) sites with risk of OSF among areca nut chewers in the Northern India population. A total of 95 histopathologically confirmed cases of OSF with history of areca nut chewing not less than 1 year and 80, age and sex matched controls without any clinical signs and symptoms of OSF with areca nut chewing habit not less than 1 year were enrolled. DNA was extracted from peripheral blood samples and polymorphisms were analyzed by PCR-RFLP method. Gene polymorphism of CYP1A1 at NcoI site was observed to be significantly higher (p = 0.016) in cases of OSF when compared to controls. Association of CYP1A1 gene polymorphism at NcoI site and the risk of OSF (Odd's Ratio = 2.275) was also observed to be significant. However, no such association was observed for the CYP2E1 gene polymorphism (Odd's Ratio = 0.815). Our results suggest that the CYP1A1 gene polymorphism at the NcoI site confers an increased risk for OSF.
- Balaji L, Singh KB, Bhaskar LVKS (2011). Genetic Polymorphisms of the CYP2E1 gene do not contribute to oral cancer susceptibility in South Indians. Asian Pac J Cancer Prev, 12, 1523-7.
- Bouchardy C, Hirvonen A, Coutelle C, et al (2000). Role of alcohol dehydrogenase 3 and cytochrome P-4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract. Int J Cancer, 87, 734-40. https://doi.org/10.1002/1097-0215(20000901)87:5<734::AID-IJC17>3.0.CO;2-E
- Buch SC, Nazar-SV, Joel L, Weissfeld MR (2008), Case control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes. Head Neck, 30, 1139-47. https://doi.org/10.1002/hed.20867
- Chaudhuri SR, Mukherjee S, Paul RR, Halder A, Chaudhuri K (2013). CYP1A1 and CYP2E1 gene polymorphisms may increase susceptibility to oral submucous fibrosis among betel chewers of Eastern India. Gene, 513, 268-71. https://doi.org/10.1016/j.gene.2012.10.043
- Ghosh T, Gupta S, Bajpai P, et al (2012). Association of CYP1A1, GSTM1, and GSTT1 gene polymorphism with risk of oral submucous fibrosis in a section of North Indian population. Mol Biol Rep, 39, 9383-9. https://doi.org/10.1007/s11033-012-1802-x
- Gonzalez MV, Alvarez V, Pello MF, et al (1998). Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer. J Clin Pathol, 51, 294-98. https://doi.org/10.1136/jcp.51.4.294
- Hazarey VK, Erlewad DM, Mundhe KA, Ughade SN (2007). Oral submucous fibrosis: a study of 1000 cases from central India. J Oral Pathol Med, 36, 12-17.
- Hebbar PB, Sheshaprasad R, Gurudath S, Pai A, Sujatha D (2014). Oral submucous fibrosis in India: Are we progressing? Indian J Cancer, 51, 222- 6. https://doi.org/10.4103/0019-509X.146724
- Joshi P, Dutta S, Chaturvedi P, Nair S (2014). Head and neck cancers in developing countries. Rambam Maimonides Med J, 5, 9.
- Kao SY, Wu CH, Lin SC (2002). Genetic polymorphism of cytochrome P-4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking / betel use. J Oral Pathol Med, 31, 505-11. https://doi.org/10.1034/j.1600-0714.2002.00158.x
- Liu S, Park JY, Schantz SP, Stern JC, Lazarus P (2001). Elucidation of CYP2E1 5' regulatory RsaI/PstI allelic variants and their role for cancer. Oral Oncol, 37, 437-45. https://doi.org/10.1016/S1368-8375(00)00099-3
- Lu D, Yu X, Du Y (2011). Meta-analyses of the effect of cytochrome P450 2E1 gene polymorphism on the risk of head and neck cancer. Mol Biol Rep, 38, 2409-16. https://doi.org/10.1007/s11033-010-0375-9
- Li N, Jian X, Hu Y, et al (2008). Discovery of novel biomarkers in oral submucous fibrosis by microarray analysis. Cancer Epidemiol. Biomarkers Prev, 17, 2249-59. https://doi.org/10.1158/1055-9965.EPI-07-2908
- Lin CY, Pan TS, Ting CC, et al (2013). Cytochrome p450 metabolism of betel quid derived compounds: implications forte development of prevention strategies for oral and pharyngeal cancers. Sci World J, 2013, 1-11.
- Mathew P, Austin RD, Varghese SS, kumar MAD (2014). Role of areca nut and its commercial products in oral submucous fibrosis- a review. J Adv Med Dent Sci Res, 2, 192-200.
- Mortazavi H, Baharvand M, Mehdipour M (2014). Oral potentially malignant disorders:an overview of more than 20 entities. J Dent Res Dent Clin Dent Prospects, 8, 6-14.
- Mukherjee S, Bhowmik AD, Choudhury RP, et al (2012). Association of XRCC1, XRCC3, and NAT2 polymorphisms with the risk of oral submucous fibrosis among eastern Indian population. J Oral Pathol Med, 41, 292-302. https://doi.org/10.1111/j.1600-0714.2011.01097.x
- Nigam NK, Aravinda K, Dhillon M, et al (2014). Prevalence of oral submucous fibrosis among habitual gutkha and areca nut chewers in Moradabad district. J Oral Biol Craniofac Res, 4, 8-13. https://doi.org/10.1016/j.jobcr.2013.10.005
- Pandya S, Chaudhary AK, Singh M, Mehrotra R (2009). Correlation of histopathological diagnosis with habits and clinical findings in oral sub mucous fibrosis. Head Neck Oncol, 1, 10. https://doi.org/10.1186/1758-3284-1-10
- Pindborg JJ, Mehta FS, Gupta PC, Daftary DK (1968). Prevalence of oral submucous fibrosis among 50,915 Indian villagers. Br J Cancer, 22, 646-54. https://doi.org/10.1038/bjc.1968.76
- Rodriguez MH, Barja N (2012). Role of cytochrome P-450 genetic polymorphisms in oral carcinogenesis. J Oral Pathol Med, 41, 1-8. https://doi.org/10.1111/j.1600-0714.2011.01067.x
- Ruwali M, Khan AJ, Shah PP, et al (2009). Cytochrome P450 2E1 and head and neck cancer: interaction with genetic and environmental risk factors. Environ Mol Mutagen, 50, 473-82. https://doi.org/10.1002/em.20488
- Sudarshan R, Annigeri RG, Vijayabala SG (2012). Pathogenesis of Oral Submucous Fibrosis: The Past and Current Concepts. Int J Oral Maxillo fac Pathol, 3, 27-36.
- Tanwir F, Akhlaq H (2011). Oral submucous fibrosis: a chronic deliberating disease of oral cavity. Iranian J Pathol, 6, 165-72.
- Tang K, Li Y, Zhang Z, et al (2010). The PstI/RsaI and DraI polymorphisms of CYP2E1 and head and neck cancer risk: a meta-analysis based on 21 case-control studies. BMC Cancer, 10, 575-81. https://doi.org/10.1186/1471-2407-10-575
- Vargas-Ferreira F, Nedel F, Etges A, et al (2012). Etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers: a brief approach. Braz Dent J, 23, 586-90. https://doi.org/10.1590/S0103-64402012000500020