Abstract
Genetic alterations in the genes expressing drug metabolizing enzymes can make an individual susceptible to various cancers. This study detects the polymorphisms at CYP1A1, GSTM1, and GSTT1 genes in a section of North Indian population and determines the susceptibility to oral submucous fibrosis (OSF). In this case–control study one hundred and two OSF patients were genotyped to detect the GSTM1, GSTT1, CYP1A1 polymorphism. Two hundred healthy controls were also included. Genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) approach. The frequency of GSTM1 and GSTT1 genotype was higher in OSF patients, as compared to controls. A trend risk analysis showed 7.6 fold increase in risk, when both the genes were absent. The frequency of CYP1A1 (m1) and CYP1A1 (m2) genotypes was higher in controls. No polymorphic alleles were detected in the m4 site. CYP1A1 (m1) wild genotype in the absence of GSTM1 null genotype, falls under the highest risk group (OR 3.74). Our findings suggest that CYP1A1 (m1) genotype and (m2) genotype singly acts as a protective factor but in the absence of GSTM1 and/or GSTT1 gene significantly alters risk towards OSF.
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Wahi PN, Kapur VL, Luthra UK, Srivastava MC (1996) Submucous fibrosis of the oral cavity. 2. Studies on epidemiology. Bull World Health Organ 35:793–799
Devasena A, Chaubal PC, Kennan S, Bhisey RA, Mahimkar MB (2007) Susceptibility to Oral Cancer by Genetic Polymorphisms at CYP1A1, GSTM1 and GSTT1 Loci among Indians: tobacco exposure as a risk modulator. Carcinogenesis 28:1455–1462
Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K (2000) Genetic polymorphism of CYP genes, alone or in combination, as a risk modifier of tobacco-related cancers. Cancer Epidemiol Biomarkers Prev 9:23–28
Tilakratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S (2006) Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol 42:561–568
Hirvonen A (1999) Polymorphism of xenobiotic-metabolizing enzymes and susceptibility to cancer. Environ Health Perspect 107:37–47
Mahmoud S, Labib DA, Khalifa RH, Abu RE (2010) CYP1A1, GSTM1 and GSTT1 Genetic Polymorphism in Egyptian Chronic Myeloid Leukemia Patients. Research Journal of Immunology. 3:12–21
Agrawal D, Gupta S, Agarwal D, Gupta OP, Agarwal M (2010) Role of GSTM1 and GSTT1 polymorphism: susceptibility to oral submucous fibrosis in the north Indian population. Oncology 79:181–186
Hirata H, Hinoda Y, Okayama N, Suehiro Y, Kawamoto K, Kikuno N et al (2008) CYP1A1, SULT1A1, SULT1E1 polymorphism are risk factors for endometrial cancer susceptibility. Cancer 112:1964–1973
Varela-Lema L, Ruano-Ravina A, Juiz Crespo MA, Kelsey KT, Loidi L, Barros-Dios JM (2008) CYP1A1, mEH, and GSTM1 polymophisms and risk of oral and pharyngeal cancer: a Spanish case-control study. J Oncol. doi:10.1155/2008/741310
Coles B, Ketterer B (1990) The role of glutathione and glutathione transferases in chemical carcinogenesis. Crit Rev Biochem Mol Biol 25:47–70
Zhou X, Cai L, Xiang Z, Li Q, Zang X (2009) GSTM1 and GSTT1 polymorphisms and nasopharyngeal cancer risk: an evidence-based meta-analysis. J Exp Clin Cancer Res 28(1):46
Buch SC, Notani PN, Bhisey RA (2002) Polymorphism at GSTM1, GSTM3 and GSTT1 gene loci and susceptibility to oral cancer in an Indian population. Carcinogenesis 23:803–807
Raimondi S, Paracchini V, Autrup H, Barros-Dios JM, Benhamou S, Boffetta P et al (2006) Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review. Am J Epidemiol 164:1027–1042
Sreeja L, Syamala V, Hariharan S, Madhavan J, Devan SC, Ankathil R (2006) Possible risk modification by CYP1A1, GSTM1, and GSTT1 gene polymorphism in lung cancer susceptibility in a South Indian population. J Hum Genet 50:618–627
Cascorbi I, Brockmoller J, Roots I (1996) A C4887A polymorphism in Exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility. Cancer Res 56:4965–4968
Peterson DD, Mckinney CE, Ikeya K, Smith HH, Bale AE, McBride OW et al (1991) Human CYPIA I Gene: cosegregation of the enzyme inducibility phenotype and an RFLP. Am J Hum Genet 48:720–725
Cosma GN, Crofts F, Currie D et al (1993) Racial differences in restriction fragment length polymorphism and mRNA inducibility in human CYP1A1 gene. Cancer Epidemiol Biomarkers Prev 2:53–57
Whittington a, Vichai V, Webb G, Baker RT, Pearson WR, Board PG (1999) Gene structure, expression and chromosomal localization of murine theta class glutathione transferase mGSTT1-1. Biochem J 337:141–151
Meyer DJ, Coles B, Pemble SE, Gilmore KS, Fraser GM, Ketterer B (1991) Theta, a new class of glutathione transferases purified from rat and man. Biochem J 274:409–414
Roots I, Drakoulis N, Brockmo¨ller J (1992) Polymorphic enzymes and cancer risk: concepts, methodology and datareview. In: Kalow W (ed) Pharmacogenetics of drug metabolism. Pergamon Presse, New York, pp 815–41
Amtha R, Ching CK, Zain R, Razak IA, Basuki B, Roeslan BO et al (2009) GSTM1, GSTT1 and CYP1A1 polymorphism and risk of oral cancer: a case-control study in Jakarta, Indonesia. Asian Pac J Cancer Prev 10:21–26
Nosheen M, Ishrat M, Malik FA, Baig RM, Kayani MA (2010) Association of GSTM1 and GSTT1 gene deletions with risk of head and neck cancer in Pakistan: a case control study. Asian Pac J Cancer Prev 11:881–885
Gronau S, Koenig-Greger D, Jerg M, Riechelmann H (2003) Gene polymorphisms in detoxification enzymes as susceptibility factor for head and neck cancer? Otolaryngol Head Neck Surg 128:674–680
Sreelekha TT, Ramadas K, Pandey M, NalinaKumari KR, Pillai MR (2001) Genetic polymorphism of CYP1A1, GSTM1, and GSTT1 genes in Indian oral cancer. Oral Oncol 37:593–598
Nair UJ, Nair J, Matthew B, Bartsch H (1999) Glutathione S-transferase M1 and T1 null genotypes as a risk factors for oral leukoplakia in ethnic betel quid/tobacco chewers. Carcinogenesis 20:743–748
Saadat M, Farhud DD, Saadat I (2001) Frequency of glutathione S-transferase M1 (GSTM1) and GSTT1 null genotypes in Fars population (South of Iran). Iran J Publ Health 30:83–86
Kumar V, Singh S, Yadav CS, Ahmed RS, Gupta S, Pasha ST et al (2010) CYP1A1 and CYP3A4 polymorphic variations in Delhi population of Northern India. Environ Toxicol Pharamacol 29:126–130
Song N, Tan W, Xing D, Lin D (2002) CYP1A1 polymorphism and risk of lung cancer in relation to tobacco smoking: a case control study in China. Carcinogenesis 22:11–16
Cordero K, Espinoza I, Caceres D, Roco A, Mirada C, Squicciarini V et al (2010) Oral cancer susceptibility associated with the CYP1A1 and GSTM1 genotypes in Chilean individuals. Oncol Lett 1:549–553
Park JY, Muscat JE, Ren Q, Schantz SP, Harwick D, Stern JC et al (1997) CYP1A1 and GSTM1 polymorphism and oral cancer risk. Cancer Epidemiol Biomarkers Prev 6:791–797
Sabitha K, Reddy MV, Jamil K (2010) Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer. Cancer Epidemiol 34:587–592
Katoh T, Kaneko S, Kohshi K, Munaka M, Kitagawa K, Kunugita N et al (1999) Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and oral cavity cancer. Int J Cancer 83:606–609
Matthias C, Bockmuhl U, Jahnke V, Harries LW, Wolf CR, Jones PW et al (1998) The glutathione S-transferase GSTP1 polymorphism: effects on susceptibility to oral/pharyngeal and laryngeal carcinomas. Pharmacogenetics 8:1
Acknowledgments
The authors wish to thank the director, Indian Institute of Toxicology Research, Lucknow, for his support. We are thankful to Deepmala Yadav (project assistant), and Ranjeeta Singh (Summer Trainee) for helping with the experiment. We acknowledge the cooperation received from all the subjects who participated in the study. The financial support from the CSIR Suprainstitutional Project (SIP-08) in carrying out this study is also gratefully acknowledged.
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Ghosh, T., Gupta, S., Bajpai, P. et al. 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, 9383–9389 (2012). https://doi.org/10.1007/s11033-012-1802-x
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DOI: https://doi.org/10.1007/s11033-012-1802-x