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. 2012 May 3;2(1):4–9. doi: 10.1016/S2212-4268(12)60003-7

Association of mitochondrial deoxyribonucleic acid mutation with polymorphism in CYP2E1 gene in oral carcinogenesis

Rahul Pandey a, Divya Mehrotra b,*, Carlo Catapano c, Vimal Choubey d, Rajiv Sarin e, Abbas Ali Mahdi f, Stuti Singh g
PMCID: PMC3941659  PMID: 25756024

Abstract

Background

Oral carcinogenesis is a complex process affected by genetic as well as environmental factors. CYP2E1 gene is involved in metabolism of number of compounds and carcinogens. Its normal functioning is required for homeostasis of free radical. Mitochondrial deoxyribonucleic acid (mtDNA) is 10–100 times more susceptible to damage than nuclear DNA. Mitochondrial DNA large scale deletions are well documented in oral cancer. However, the relationship between CYP2E1 gene polymorphisms and mtDNA damage is still not documented in literature.

Materials and Methods

Case–control study involving 50 subjects was carried out. Deoxyribonucleic acid extraction was done from study subject tissue samples. Restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) amplification was done to confirm CYP2E1 gene polymorphisms. The PCR amplification was done for mtDNA 4977 bp deletion. Statistical analysis was carried out using SPSS version 11.5 with χ2 tests.

Results

c1c1 and DD polymorphisms are prevalent in North Indian population having oral cancer. These polymorphisms are significantly associated with mtDNA 4977 bp deletion.

Conclusion

Mitochondrial DNA damage induced by wild CYP2E1 forms and imperfect DNA repair in mtDNA may act synergistically to greatly enhance oral cancer risk.

Keywords: CYP2E1, DNA, mitochondria, oral cancer

Full Text

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References

  • 1.Stewart BW, Kleihues P. World Cancer Report. WHO International Agency for Research on Cancer; Lyon: 2003. pp. 1–351. [Google Scholar]
  • 2.Brennan P, Boffetta P. Mechanistic considerations in the molecular epidemiology of head and neck cancer. IARC Sci Publ. 2004;157:393–414. [PubMed] [Google Scholar]
  • 3.Bartsch H, Nair U, Risch A, Rojas M, Wikman H, Alexandrov K. Genetic polymorphisms of CYP gene, alone or in combination as a risk modifier of tobacco related cancers. Cancer Epidemiol Biomarker Prev. 2000;9:3–28. [PubMed] [Google Scholar]
  • 4.Danko IM, Chaschin NA. Association of CYP2E1 gene polymorphism with predisposition to cancer development. Exp Oncol. 2005;27:248–256. [PubMed] [Google Scholar]
  • 5.Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Scott EM. Facile detection of mitochondrial DNA mutations in tumours and bodily fluids. Science. 2000;287:2017–2019. doi: 10.1126/science.287.5460.2017. [DOI] [PubMed] [Google Scholar]
  • 6.Copeland WC, Wachsman JT, Johnson FM, Penta JS. Mitochondrial DNA alterations in cancer. Cancer Invest. 2002;20:557–569. doi: 10.1081/cnv-120002155. [DOI] [PubMed] [Google Scholar]
  • 7.Lee HC, Lu CY, Fahn HJ, Wei YH. Aging- and smoking-associated alteration in the relative content of mitochondrial DNA in human lung. FEBS Lett. 1998;441:292–296. doi: 10.1016/s0014-5793(98)01564-6. [DOI] [PubMed] [Google Scholar]
  • 8.Kim MM, Glazer CA, Mambo E, Chatterjee A, Zhao M, Sidransky D. Head and neck cancer cell lines exhibit differential mitochondrial repair deficiency in response to 4NQO. Oral Oncol. 2006;42:201–207. doi: 10.1016/j.oraloncology.2005.07.004. [DOI] [PubMed] [Google Scholar]
  • 9.Liu S, Park JY, Schantz SP, Stern JC, Lazarus P. Elucidation of CYP2E1 5′ regultory Rsal/PstI allelic variants and their role in risk for oral cancer. Oral Oncol. 2001;37:437–445. doi: 10.1016/s1368-8375(00)00099-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Vidal F, Lorenzo A, Auguet T. Genetic polymorphisms of ADH2, ADH3, CYP4502E1Dra-I and Pst-I, and ALDH2 in Spanish men: lack of association with alcoholism and alcoholic liver disease. J Hepatol. 2004;41:744–750. doi: 10.1016/j.jhep.2003.06.003. [DOI] [PubMed] [Google Scholar]
  • 11.Wong LJC, Liang MH, Kwon H. Comprehensive scanning of the whole mitochondrial genome for mutations. Clin Chem. 2002;48:1901–1912. [PubMed] [Google Scholar]
  • 12.Shiu MN, Chan TH, Chang SH, Hahn LJ. Risk factors for leukoplakia and malignant transformation to oral carcinoma: a leukoplakia cohort in Taiwan. Br J Cancer. 2000;82:1871–1874. doi: 10.1054/bjoc.2000.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Guengerich FP, Kim DH, Iwasaki M. Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol. 1991;4:168–179. doi: 10.1021/tx00020a008. [DOI] [PubMed] [Google Scholar]
  • 14.Hayashi S, Watanabe J, Kawajiri K. Genetic polymorphisms in the 5′-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem. 1991;110:559–565. doi: 10.1093/oxfordjournals.jbchem.a123619. [DOI] [PubMed] [Google Scholar]
  • 15.Uematsu F, Kikuchi H, Motomiya M, Abe T, Sagami I, Watanabe M. Association between restriction fragment length polymorphism of the human cytochrome P45011E1 gene and susceptibility to lung cancer. Jpn J Cancer Res. 1991;82:254–256. doi: 10.1111/j.1349-7006.1991.tb01838.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Hung HC, Chuang J, Chien YC. Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer. Cancer Epidemiol Biomarkers Prev. 1997;6:901–905. [PubMed] [Google Scholar]
  • 17.Liu S, Park JY, Schantz SP, Stern JC, Lazarus P. Elucidation of CYP2E1 5′ regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer. Oral Oncol. 2001;37:437–445. doi: 10.1016/s1368-8375(00)00099-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Uematsu F, Ikawa S, Kikuchi S. Restriction fragment length polymorphism of the human CYP2E1 (cytochrome P450IIE1) gene and susceptibility to lung cancer: possible relevance to low smoking exposure. Pharmacogenetics. 1994;4:58–63. doi: 10.1097/00008571-199404000-00002. [DOI] [PubMed] [Google Scholar]
  • 19.Matthias C, Bockmuhl U, Jahnke V. Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: studies in upper aerodigestive tract cancers. Pharmacogenetics. 1998;8:91–100. [PubMed] [Google Scholar]
  • 20.Sikdar N, Mahmud SK, Paul RR, Roy B. Polymorphism in CYP1A1 and CYP2E1 genes and susceptibility to leukoplakia in Indian tobacco users. Cancer Lett. 2003;195:33–42. doi: 10.1016/s0304-3835(03)00156-3. [DOI] [PubMed] [Google Scholar]
  • 21.Hildesheim A, Anderson LM, Chen CJ. CYP2E1 genetic polymorphisms and risk of nasopharyngeal carcinoma in Taiwan. J Natl Cancer Inst. 1997;89:1207–1212. doi: 10.1093/jnci/89.16.1207. [DOI] [PubMed] [Google Scholar]
  • 22.Sugimura T, Kumimoto H, Tohnai I. Gene-environment interaction involved in oral carcinogenesis: Molecular epidemiological study for metabolic and DNA repair gene polymorphisms. J Oral Pathol Med. 2006;35:11–18. doi: 10.1111/j.1600-0714.2005.00364.x. [DOI] [PubMed] [Google Scholar]
  • 23.Soya SS, Vinod T, Reddy KS, Gopalakrishnan S, Adithan C. CYP2E1 polymorphisms and gene-environment interactions in the risk of upper aerodigestive tract cancers among Indians. Pharmacogenomics. 2008;9:551–560. doi: 10.2217/14622416.9.5.551. [DOI] [PubMed] [Google Scholar]
  • 24.Garte S, Gaspari L, Alexandrie AK. Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev. 2001;10:1239–1248. [PubMed] [Google Scholar]

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