Abstract
Many studies have investigated the association between the CYP2E1 5′-flanking region (RsaI/PstI) polymorphism and head and neck cancer susceptibility, but the results were conflicting. In this meta-analysis, we assessed 24 published studies involving 12,562 subjects of the association between CYP2E1 RsaI/PstI polymorphism and head and neck cancer risk. Using the fixed effects model, we found significant association between PstI/RsaI polymorphism and head and neck cancer risk [OR = 1.11 (95%CI: 1.00–1.22) for c2 allele (P = 0.04) and OR = 1.57 (95% CI: 1.14–2.15) for c2 homozygous (P = 0.006) compared with wild type homozygote]. Significant results were also found in East Asians and Mix populations when stratified by ethnicity. However, no significant associations were found for Caucasians in all genetic models. Stratified analyses according to source of controls, significant associations were found only in hospital base controls. In the subgroup analyses by tumor types, significant association was detected only in oral cancer group, while no significant associations among laryngeal- or pharyngeal- cancer subgroup. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism may be a risk factor for head and neck cancer in Asians and Mix population, and that different carcinogenic processes involved in the genesis of various tumor types may exist.




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Abbreviations
- CI:
-
Confidence interval
- HNSCC:
-
Squamous cell carcinoma of head and neck
- HWE:
-
Hardy–Weinberg equilibrium
- OR:
-
Odds ratio
References
Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S (1998) Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res 18:4779–4786
Blot WJ, McLaughlin JK et al (1998) Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48:3282–3287
Lewin F, Norell SE, Johansson H, Gustavsson P, Wennerberg J, Biörklund A, Rutqvist LE (1998) Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case–referent study in Sweden. Cancer 82:1367–1375
Maier H, Dietz A, Gewelke U, Heller WD, Weidauer H (1992) Tobacco and alcohol and the risk of head and neck cancer. Clin Invest 70:320–327
Muscat JE, Wynder EL (1992) Tobacco, alcohol, asbestos and occupational risk factors for laryngeal cancer. Cancer 69:2244–2251
Yamazaki H, Inui Y, Yun C, Guengerich FP, Shimada T (1992) Cytochrome P4502E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes. Carcinogenesis 13:1789–1794
Bellec G, Dreano Y, Lozach P, Menez JF, Berthou F (1996) Cytochrome P450 metabolic dealkylation of nine N-nitroso-dialkylamines by human liver microsomes. Carcinogenesis 17:2029–2034
Hoffmann D, Hecht SS (1985) Nicotine-derived N-nitrosamines and tobacco-related cancer: current status and future directions. Cancer Res 45:935–944
Hecht SS, Hoffmann D (1988) Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis 9:875–884
Hayashi SI, Watanabe J, Kawajiri K (1991) Genetic polymorphisms in the 5′-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem 110:559–565
Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. British Med J 315:629–634
Lucas D, Menez C, Floch F, Gourlaouen Y, Sparfel O, Joannet I et al (1996) Cytochromes P4502E1 and P4501A1 genotypes and susceptibility to cirrhosis or upper aero digestive tract cancer in alcoholic Caucasians. Alcohol Clin Exp Res 20:1033–1037
Hung HC, Chuang J, Chien YC, Chern HD, Chiang CP, Kuo YS et al (1997) Genetic polymorphisms of CYP2E1, GSTM1, and GSTM3; environmental factors and risk of oral cancer. Cancer Epidemiol Biomarkers Prev 6:901–905
Hildesheim A, Anderson LM, Chen CJ et al (1997) CYP2E1 genetic polymorphisms and risk of nasopharyngeal carcinoma in Taiwan. J Natl Cancer Inst 89:1207–1212
Matthias C, Bockmühl U, Jahnke V, Jones PW, Hayes JD, Alldersea J, Gilford J, Bailey L, Bath J, Worrall SF, Hand P, Fryer AA, Strange RC (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(2):91–100
González MV, Alvarez V, Pello MF, Menéndez MJ, Suárez 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(4):294–298
Katoh T, Kaneko S, Kohshi K, Munaka M, Kitagawa K, Kunugita N, Ikemura K, Kawamoto T (1999) Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and oral cavity cancer. Int J Cancer 83:606–609
Morita S, Yano M, Tsujinaka T, Akiyama Y, Taniguchi M, Kaneko K, Miki H, Fujii T, Yoshino K, Kusuoka H, Monden M (1999) Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to head-and-neck squamous-cell carcinoma. Int J Cancer 80:685–688
Bouchardy C, Hirvonen A, Coutelle C, Ward PJ, Dayer P, Benhamou S (2000) Role of alcohol dehydrogenase 3 and cytochrome P-4502E1 genotypes in susceptibility to cancers of the upper aerodigestive tract. Int J Cancer 87:734–740
Kongruttanachok N, Sukdikul S, Setavarin S et al (2001) Cytochrome P450 2E1 polymorphism and nasopharyngeal carcinoma development in Thailand: a correlative study. BMC Cancer 1:4
Liu S, Park JY, Schantz SP, Stern JC, Lazarus P (2001) Elucidation of CYP2E1 5′ regulatory RsaI/Pstl allelic variants and their role in risk for oral cancer. Oral Oncol 37:437–445
Neuhaus T, Ko Y-D, Lorenzen K, Fronhoffs S, Harth V, Bröde P, Vetter H, Bolt HM, Pesch B, Brüning T (2004) Association of cytochrome P450 2E1 polymorphisms and head and neck squamous cell cancer. Toxicol Lett 151:273–282
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
Yang XR, Diehl S, Pfeiffer R, Chen CJ, Hsu WL, Dosemeci M, Cheng YJ, Sun B, Goldstein AM, Hildesheim A (2005) Evaluation of risk factors for nasopharyngeal carcinoma in high-risk nasopharyngeal carcinoma families in Taiwan. Cancer Epidemiol Biomarkers Prev 14:900–905
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(6):632–637
Li G, Liu Z, Sturgis EM, Chamberlain RM, Spitz MR, Wei Q (2005) CYP2E1 G1532C, NQO1 Pro187Ser, and CYP1B1 Val432Leu polymorphisms are not associated with risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomarkers Prev 14:1034–1036
Sugimura T, Kumimoto H, Tohnai I, Fukui T, Matsuo K, Tsurusako S et al (2006) Gene–environment interaction involved in oral carcinogenesis: molecular epidemiological study for metabolic and DNA repair gene polymorphisms. J Oral Pathol Med 35:11–18
Gattá GJF, de Carvalho MB, Siraque MS et al (2006) Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 associated with head and neck cancer. Head Neck 28(9):819–826
Boccia S, Cadoni G, Sayed-Tabatabaei FA, Volante M, Arzani D, De Lauretis A, Cattel C, Almadori G, van Duijn CM, Paludetti G, Ricciardi G (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
Soya SS, Vinod T, Reddy KS, Gopalakrishnan S, Adithan C (2008) CYP2E1 polymorphisms and gene-environment interactions in the risk of upper aerodigestive tract cancers among Indians. Pharmacogenomics 9:551–560
Shama C, Buch, Valle, Nazar-Stewart, Joel L, MarjorieRomkes, Weissfeld (2008) Case-control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes. Head Neck 30:1139–1147
Ruwali M, Khan AJ, Shah PP, Singh AP, Pant MC, Parmar D (2009) Cytochrome P450 2E1 and head and neck cancer: interaction with genetic and environmental risk factors. Environ Mol Mutagen 50:473–482
Olivieri EH, da Silva SD, Mendonça FF, Urata YN, Vidal DO, Faria MD, Nishimoto IN, Rainho CA, Kowalski LP, Rogatto SR (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):e73–e79
Tai J, Yang M, Ni X, Yu D, Fang J, Tan W, Huang Z, Wu C, Chen X, Wang G, Zhou W, Chen X, Zhang W, Ma L, Lin D, Han D (2010) Genetic polymorphisms in cytochrome P450 genes are associated with an increased risk of squamous cell carcinoma of the larynx and hypopharynx in a Chinese population. Cancer Genet Cytogenet 196(1):76–82
Garcia SM, Curioni OA, de Carvalho MB, Gattás GJ (2010) Polymorphisms in alcohol metabolizing genes and the risk of head and neck cancer in a Brazilian population. Alcohol Alcohol 45(1):6–12
Hirschhorn JN, Lohmueller K, Byrne E (2002) A comprehensive review of genetic association studies. Genet Med 4:45–61
Lucas D, Menez C, Girre C, Berthou F, Bodenez P, Joannet I et al (1995) Cytochrome P4502E1 genotype and chloroxazone metabolism in healthy and alcoholic Caucasian subjects. Pharmacogenetics 5:298–304
Kim RB, Yamazaki H, Chiba K, O’Shea D, Mimura M, Guengerich FP et al (1996) In vivo and in vitro characterization of CYP2E1 activity in Japanese and Caucasians. J Pharmacol Exp Ther 279:4–11
Rodriguez C, Calle EE, Miracle-McMahill HL, Tatham LM, Wingo PA, Thun MJ et al (1997) Family history and risk of fatal prostate cancer. Epidemiology 8:653–659
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Lu, D., Yu, X. & Du, Y. Meta-analyses of the effect of cytochrome P450 2E1 gene polymorphism on the risk of head and neck cancer. Mol Biol Rep 38, 2409–2416 (2011). https://doi.org/10.1007/s11033-010-0375-9
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DOI: https://doi.org/10.1007/s11033-010-0375-9

