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Polymorphisms of the CYP1A1 and CYP2E1 genes in head and neck squamous cell carcinoma risk

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Abstract

Polymorphisms in genes that encode P450 cytochrome enzymes may increase carcinogen activation or decrease their inactivation and consequently, promote the development of cancer. The aims of this study were to identify the MspI-CYP1A1, PstI-CYP2E1 and DraI-CYP2E1 polymorphisms in patients with head and neck cancer and to compare with individuals without cancer; to evaluate the association of these polymorphisms with risk factors and clinical histopathological parameters. In the study group, 313 patients were evaluated for CYP1A1, 217 for CYP2E1 (PstI) and 211 for CYP2E1 (DraI) and in the control group 417, 334 and 374 individuals, respectively. Molecular analysis was performed by PCR–RFLP technique, and chi-square and multiple logistic regression tests were used for statistical analysis. The result of analysis regarding individuals evaluated for CYP1A1 (MspI) showed that age (OR: 8.15; 95% CI 5.57–11.92) and smoking (OR: 5.37; 95% CI 3.52–8.21) were predictors for the disease; for the CYP2E1 (PstI and DraI), there were associations with age (PstI-OR: 9.10; 95% CI 5.86–14.14/DraI-OR: 8.07; 95% CI 5.12–12.72), smoking (PstI-OR: 4.10; 95% CI 2.44–6.89/DraI-OR: 5.73; 95% CI 3.34–9.82), alcohol (PstI-OR: 1.93; 95% CI 1.18–3.16/DraI-OR: 1.69; 95% CI 1.02–2.81), respectively, with disease development. CYP2E1 (PstI) was less frequent in patient group (OR: 0.48; 95% CI 0.23–0.98). Regarding clinical histopathological parameters, CYP1A1 polymorphism was less frequent in the larynx primary anatomic site (OR = 0.45; 95% CI = 0.28–0.73; P = 0.014). In conclusion, we confirm that age, smoking and alcohol consumption are risk factors for this disease and the polymorphisms investigated have no association with the development of head and neck cancer.

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References

  1. Ragin CC, Modugno F, Gollin SM (2007) The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J Dent Res 86:104

    Article  PubMed  CAS  Google Scholar 

  2. Olivieri EHR, da Silva SD, Mendonça FF, Urata YN, Vidal DO, Faria MAM et al (2009) CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients. Oral Oncol 45(9):73–79

    Article  Google Scholar 

  3. Curado MP, Hashibe M (2009) Recent changes in the epidemiology of head and neck cancer. Curr Opin Oncol 21:194–200

    Article  PubMed  Google Scholar 

  4. Hashibe M, Brennan P, Benhamou S, Castellsague X, Chen C, Curado MP et al (2008) Alcohol drinking in never users of tobacco, cigarette smoking in never drinkers, and the risk of HNSCC: pooled analysis in the international HNSCC epidemiology consortium. J Natl Cancer Inst 99(10):777–789, 2007. Erratum in: J Natl Cancer Inst 100(3):225

    Google Scholar 

  5. Hiyama T, Yoshihara M, Tamaka S, Chayama K (2008) Genetic polymorphisms and head and neck cancer risk. Int J Oncol 32:945–973

    PubMed  CAS  Google Scholar 

  6. Zain RB (2007) Cultural and dietary risk factors of oral cancer and precancer—a brief overview. Oral Oncol 37:205–210

    Article  Google Scholar 

  7. Guengerich FP (2007) Mechanisms of cytochrome P450 substrate oxidation: minireview. J Biochem Mol Toxicol 21(4):163–168

    Article  PubMed  CAS  Google Scholar 

  8. Abbas A, Delvinquiére K, Lechevrel M, Lebailly P, Gauduchon P, Launoy G et al (2004) GSTM1, GSTT, GSTP1 and CYP1A1 genetic polymorphisms and susceptibility esophageal cancer in French population: Different pattern of squamous cell carcinoma and adenocarcinoma. World J Gastroenterol 23:3389–3393

    Google Scholar 

  9. Evans AJ, Henner WD, Eilers KM, Montalto MA, Wersinger EM, Andersen PE et al (2004) Polymorphisms of GSTT1 and related genes in head and neck cancer risk. Head Neck 26:63–70

    Article  PubMed  Google Scholar 

  10. Liu S, Park JY, Schantz SP, Stern JC, Lazarus P (2001) Elucidation of CYP2E1 5′ regulatory RsaI/PstI allelic variants and their role in risk of oral cancer. Oral Oncol 37:437–445

    Article  PubMed  CAS  Google Scholar 

  11. Harth V, Schäfer M, Abel J, Maintz L, Neuhaus T, Besuden M et al (2008) Head and neck squamous-cell cancer and its association with polymorphic enzymes of xenobiotic metabolism and repair 2. J Toxicol Environ Health 71:887–897

    Article  CAS  Google Scholar 

  12. Wunsch A, Ahda Y, Banaz-YaSar F, Sonntag B, Nieschlag E, Simoni M et al (2005) Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor. Fertil Steril 84(2):446–453

    Article  PubMed  CAS  Google Scholar 

  13. Androtsopoulos VP, Tsatsakis AM, Spandidos DA (2009) Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer 9:187

    Article  Google Scholar 

  14. Rusin P, Marckiewicz L, Majsterek I (2008) Genetic predeterminations of head and neck cancer. Postepy Hig Med Dosw 62:490–501

    Google Scholar 

  15. Božina N, Bradamante V, Lovrić M (2009) Genetic polymorphism of metabolic enzymes P450 (Cyp) as a susceptibility factor for drug response, toxicity, and cancer risk. Arh Hig Rada Toksikol 60:217–242

    Article  PubMed  Google Scholar 

  16. Gattas GJF, de Carvalho MB, Siraque MS, Curioni OA, Kohler P, Eluf-Neto J et al (2006) Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer. Head Neck 28:819–826

    Article  PubMed  Google Scholar 

  17. Liu R, Yin LH, Pu YP (2007) Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huai’an population, China. Chin Med J 120:1797–1802

    PubMed  CAS  Google Scholar 

  18. Sreeja L, Syamala V, Hariharan S, Madhavan J, Devan SC, Ankathil R (2005) Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population. J Hum Genet 50:618–627

    Article  PubMed  CAS  Google Scholar 

  19. Juárez-Cedillo T, Vallejo M, Fragoso JM, Hernández-Hernández DM, Rodríguez-Pérez JM, Sánchez-García S et al (2007) The risk of developing cervical cancer in Mexican women is associated to CYP1A1 MspI polymorphism. Eur J Cancer 43(10):1590–1595

    Article  PubMed  Google Scholar 

  20. Gajecka M, Rydzanicz M, Jaskula-Sztul R, Kujawski M, Szyfter W, Szyfter K (2005) CYP1A1, CYP2D6, CYP2E1, NAT2, GSTM1 and GSTT1 polymorphisms or their combinations are associated with the increased risk of the laryngeal squamous cell carcinoma. Mutat Res 574:112–123

    Article  PubMed  CAS  Google Scholar 

  21. Hildesheim A, Anderson LM, Chen CJ, Cheng YJ, Brinton LA, Daly AK et al (1997) CYP2E1 genetic polymorphisms and risk of nasopharyngeal carcinoma in Taiwan. J Natl Cancer 89:1207–1212

    Article  CAS  Google Scholar 

  22. Lee KJ (2003) Essential otorhinolaryngology. Head Neck Surg 8:1136

    Google Scholar 

  23. Liu CJ, Chang CS, Lui MT, Dang CW, Shih YH, Chang KW (2005) Association of GST genotypes whith age of onset and lymph node metatasis in oral squamous cell carcinoma. J Oral Pathol Med 54:475–481

    Google Scholar 

  24. Instituto Nacional do Câncer. UICC—União Internacional Contra o Câncer, 2002—TNM—Classificação de Tumores Malignos 6ª. Edição. Ministério da Saúde. Rio de Janeiro: INCA 2004

  25. Greene FL, Page DL, Fleming ID, Fritz A, Balch CM, Haller DG, Morrow M (2002) AJCC Cancer Staging Manual, 6th ed. New York, Springer

  26. Sobin LH, Wittelind CH (2000) Internacional union against cancer: TNM classification of malignant tumours, 6th edn. Wiley, New York

    Google Scholar 

  27. Ahrendt SA, Chown JT, Yang SC, Wu L, Zhang M-J, Jen J et al (2000) Alcohol consumption and cigarette smoking increase the frequency of p53 mutations in nomsmall cell lung cancer. Cancer Res 60:3155–3159

    PubMed  CAS  Google Scholar 

  28. Kjaerheim K, Gaard M, Andersen A (1998) The role of alcohol, tobacco, and dietary factors in upper aerogastric tract cancers: a prospective study of 10,900 Norwegian men. Cancer Causes Control 9(1):99–108

    Article  PubMed  CAS  Google Scholar 

  29. Miller AS, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    Article  PubMed  CAS  Google Scholar 

  30. Arvanitis DA, Goumenou AG, Matalliotaski IM, Koumantaski EE, Spandidos DA (2001) Low penetrance genes are associated with increased susceptibility to endometriosis. Fertil Steril 76:1202

    Article  PubMed  CAS  Google Scholar 

  31. Kato S, Shields PG, Caporaso NE, Hoover RN, Trump BF, Sugimura H et al (1992) Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk. Cancer Res 52:6712–6715

    PubMed  CAS  Google Scholar 

  32. Hirvonen A, Husgafvel-Pursianen K, Karjalainen A, Antilla S, Vainio H (1993) The human CYP2E1 gene and lung cancer: Dra1 and Rsa1 restriction length polymorphisms in a Finnish study population. Carcinogenesis 14:85–88

    Article  PubMed  CAS  Google Scholar 

  33. Goldstein DP, Irish JC (2005) Head and neck squamous cell carcinoma in the young patient. Curr Opin Otolar & Head Neck Surg 13:207–211

    Article  Google Scholar 

  34. Marques CFS, Koifman S, Koifman RJ, Boffetta P, Brennan P, Hatagima A (2006) Influence of CYP1A1, CYP2E1, GSTM3 and NAT2 genetic polymorphisms in oral cancer susceptibility: results from a case-control study in Rio de Janeiro. Oral Oncol 42:632–637

    Article  PubMed  CAS  Google Scholar 

  35. Galbiatti AL, Ruiz MT, Rezende Pinto D, Raposo LS, Maníglia JV, Pavarino-Bertelli EC et al. (2010) A80G polymorphism of reduced folate carrier 1 (RFC1) gene and head and neck squamous cell carcinoma etiology in Brazilian population. Mol Biol Rep. dio:10.1007/s11033-010-0204-1

  36. Boffeta P, Hashibe M (2006) Alcohol and cancer. Lancet Oncol 7:149–156

    Article  Google Scholar 

  37. Warnakulasuriya S, Sutherland G, Scully C (2008) Tobacco, oral cancer, and treatment of dependence. Oral Oncol 41:244–260

    Article  Google Scholar 

  38. Dedivitis RA, França CM, Mafra ACB, Guimarães FT, Guimarães AV (2004) Características clínicoepidemiológicas no carcinoma espinocelular de boca e orofaringe. Ver Bras Otorhinolaryngol 70:35–40

    Article  Google Scholar 

  39. Lung T, Tascau OC, Almasan HA, Muresan O (2007) Head and neck cancer, epidemiology and histological aspects Part 1: A decade′s result 1993–2002. J Craniomaxillofac Surg 35:120–125

    Article  PubMed  Google Scholar 

  40. Hershkovich O, Shafat I, Nagler RM (2007) Age-related changes in salivary antioxidant profile: possible implications for oral cancer. J Gerontol A Biol Sci Med Sci 62:361–366

    Article  PubMed  Google Scholar 

  41. Du D, Shi YH, Le GW (2010) Oxidative stress induced by high-glucose diet in liver of C57BL/6 J mice and its underlying mechanism. Mol Biol Rep 37:3833–3839

    Article  PubMed  CAS  Google Scholar 

  42. Gronau S, Koing-Greger D, jerg M, Riechelmann H (2003) Gene polymorphisms in detoxification enzymes as susceptibility factor for head and neck cancer? Otorhinolaryngol Head Neck Surg 5:674–680

    Article  Google Scholar 

  43. Buch SC, Nazar-Stewart V, Weissfeld JL, Romkers M (2008) Case-control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes. Head Neck 30:1139–1147

    Article  PubMed  Google Scholar 

  44. Singh AP, Shah PP, Ruwali M, Mathur N, Pant MC, Parmar D (2009) Related articles polymorphism in cytochrome P4501A1 is significantly associated with head and neck cancer risk. Cancer Invest 27(8):869–876

    Article  PubMed  CAS  Google Scholar 

  45. Kawajiri K, Nakachi K, Imai K, Yoshii A, Shinoda N, Watanabe J (1999) Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P4501A1 gene. FEBS Lett 263:131–133

    Article  Google Scholar 

  46. Houlston RS (2000) CYP1A1 polymorphisms and lung cancer risk: a meta-analysis. Pharmacogenetics 10(2):105–114

    Article  PubMed  CAS  Google Scholar 

  47. Taioli E, Gaspari L, Benhamou S, Boffetta P, Brockmoller J, Butkiewicz D et al (2003) Polymorphisms in CYP1A1, GSTM1, GSTT1 and lung cancer below the age of 45 years. Int J Epidemiol 32:60–63

    Article  PubMed  CAS  Google Scholar 

  48. Vineis P, Veglia F, Benhamou S, Butkiewicz D, Cascorbi I, Clapper ML et al (2003) CYP1A1 T3801 C polymorphism and lung cancer: a pooled analysis of 2451 cases and 3358 controls. Int J Cancer 104:650–657

    Article  PubMed  CAS  Google Scholar 

  49. Goodman MT, McDuffie K, Hernandez B et al (2001) CYP1A1, GSTM1, and GSTT1 polymorphisms and the risk of cervical squamous intraepithelial lesions in a multiethnic population. Gynecol Oncol 81:263–269

    Article  PubMed  CAS  Google Scholar 

  50. Cha I-H, Park JY, Chung W-Y, Choi M-A, Kim H-J, Park K-k (2007) Polymorphisms of CYP1A1 and GSTM1 genes and susceptibility to oral cancer. Yonsci Med J 48:233–239

    Article  CAS  Google Scholar 

  51. Leichsenring A, Losi-Guembarovski R, Maciel ME, Losi-Guembarovski A, Oliveira BW, Ramos G et al (2006) CYP1A1 and GSTP1 polymorphisms in an oral cancer case-control study. Braz J Med Biol Res 39(12):1569–1574

    Article  PubMed  CAS  Google Scholar 

  52. Bergheim I, Wolfgarten E, Bollschweiler E, Hölscher AH, Bode C, Parlesak A (2007) Cytochrome P450 levels are altered in patients with esophageal squamous-cell carcinoma. World J Gastroenterol 13(7):997–1002

    PubMed  CAS  Google Scholar 

  53. Matthias C, Jahnke V, Jones PW, Hoban PR, Alldersea JE, Worrall SF et al (1999) Cyclin D1, glutathione S-transferase, and cytocrome P450 genotypes and outcome in patients with upper aerodigestive tract cancers: assessment of the importance of individual genes using multivariate analysis. Cancer Epidemiol Biomakers Prev 8:815–823

    CAS  Google Scholar 

  54. 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

    Article  PubMed  CAS  Google Scholar 

  55. Neuhaus T, Ko YD, Lorenzen K, Fronhoffs S, Harth V, Bröde P et al (2004) Association of cytochrome P450 2E1 polymorphisms and head and neck squamous cell cancer. Toxicol Lett 151:273–282

    Article  PubMed  CAS  Google Scholar 

  56. Boccia S, Cadoni G, Sayed-Tabatabaei FA, Volante M, Arzani D, Lauretis A (2008) CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer. J Cancer Res Clin Oncol 134:93–100

    Article  PubMed  CAS  Google Scholar 

  57. Hildesheim A, Chen CJ, Caporaso NE, Cheng YJ, Hoover RN, Hsu MM et al (1995) Cytochrome P4502E1 genetic polymorphisms and risk of nasopharyngeal carcinoma: results from a case-control study conducted in Taiwan. Cancer Epidemiol Biomarkers Prev 4:607–610

    PubMed  CAS  Google Scholar 

  58. Kongruttanachok N, Sukdikul S, Setavarin S, Kerekhjanarong V, Supiyaphun P, Voravud N et al (2001) Cytochrome P450 2E1 polymorphism and nasopharyngeal carcinoma development in Thailand: a correlative study. BMC Cancer 1:4

    Article  PubMed  CAS  Google Scholar 

  59. Gonzalez MV, Alvarez V, Pello MF, Menendez MJ, Suarez C, Coto E (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 51:294–298

    Article  PubMed  CAS  Google Scholar 

  60. Gao CM, Takezaki T, Wu JZ, Chen MB, Liu YT, Ding JH et al (2007) CYP2E1 Rsa I polymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking. World J Gastroenterol 13:5725–5730

    PubMed  CAS  Google Scholar 

  61. Sugimura T, Kumimoto H, Tohnai I, Fukui T, Matsuo K, Tsurusako S et al (2006) Gene-environment interaction involved in oral carcinogenesis: molecular epidemio- logical study for metabolic and DNA repair gene polymorphisms. J Oral Pathol Med 35:11–18

    Article  PubMed  CAS  Google Scholar 

  62. Bouchard C, Hirvonen A, Coutelle C, Ward PJ, Dayer P, Benhamou S (2000) Role of alcohol dehydrogenase 3 and cytochrome P-450E1 genotypes in susceptibility to cancers of the upper aerodigestive tract. Int J Cancer 87:734–740

    Article  Google Scholar 

  63. Agulnik M (2007) Malignancies of head and neck: the role for molecular targeted agents. Expert Opin Ther Targets 11(2):207–217

    Google Scholar 

  64. Stwart BM, Kleihues P (2003) World cancer report. IARC Press, Lyon

    Google Scholar 

  65. Matthias C, Bockmuhl U, Jahnke V, Jones PW, Hayes JD, Alldersea J et al (1998) 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 8:91–100

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to participation of the Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES and Conselho Nacional de Desenvolvimento Cientıífico e Tecnológico-CNPq for their support and FAMERP/FUNFARME in this study.

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Authors and Affiliations

  1. Genetics and Molecular Biology Research Unit-UPGEM, São José do Rio Preto Medical School (FAMERP), São José do Rio Preto, SP, Brazil

    Nathália Moreno Cury, Anelise Russo, Ana Lívia Silva Galbiatti, Mariângela Torreglosa Ruiz, Érika Cristina Pavarino & Eny Maria Goloni-Bertollo

  2. Department of Otorhinolaryngology and Head and Neck Surgery, São José do Rio Preto Medical School (FAMERP), São José do Rio Preto, SP, Brazil

    Luiz Sérgio Raposo & José Victor Maniglia

  3. Departamento de Biologia Molecular, Faculdade de Medicina de São José do Rio Preto (FAMERP), Av. Brigadeiro Faria Lima, 5416, São José do Rio Preto, SP, CEP 15090-000, Brazil

    Eny Maria Goloni-Bertollo

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  1. Nathália Moreno Cury
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  2. Anelise Russo
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Cury, N.M., Russo, A., Galbiatti, A.L.S. et al. Polymorphisms of the CYP1A1 and CYP2E1 genes in head and neck squamous cell carcinoma risk. Mol Biol Rep 39, 1055–1063 (2012). https://doi.org/10.1007/s11033-011-0831-1

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