Tumor Biology

, Volume 34, Issue 2, pp 1215–1224 | Cite as

CYP2E1 polymorphisms and colorectal cancer risk: a HuGE systematic review and meta-analysis

  • Ou Jiang
  • Rongxing Zhou
  • Daoquan Wu
  • Yu Liu
  • Wenjian Wu
  • Nansheng Cheng
Research Article


Studies investigating the associations between Cytochrome P4502E1 (CYP2E1) polymorphisms and colorectal cancer (CRC) risk report conflicting results. We conducted a meta-analysis to assess the association between CYP2E1 gene Rsa I/Pst I, Dral T/A and 96-bp insertion polymorphisms and CRC susceptibility. Two investigators independently searched the Medline, Embase, CNKI, Wanfang, and Chinese Biomedicine Databases. Summary odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for CYP2E1 polymorphisms and CRC were calculated in a fixed-effect model (the Mantel–Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Ultimately, 12, 5, and 4 studies were found to be eligible for meta-analyses of Rsa I/Pst I, Dral T/A, and 96-bp insertion polymorphisms, respectively. Our analysis suggested that the variant genotype of Rsa I/Pst I were associated with a significantly increased CRC risk (c2/c2 vs. c1/c1, OR = 1.36, 95 % CI = 1.04–1.77; recessive model, OR = 1.35, 95 % CI = 1.04–1.75). Moreover, similar results were observed between CYP2E1 96-bp insertion polymorphism and CRC risk (dominant model, OR = 1.25, 95 % CI = 1.07–1.45), while no association was observed between CYP2E1 Dral T/A polymorphism and CRC susceptibility in any genetic model. No publication bias was found in the present study. This meta-analysis shows that CYP2E1 Rsa I/Pst I and 96-bp insertion polymorphisms may be associated with CRC risk. The CYP2E1 Dral T/A polymorphism was not detected to be related to the risk for CRC.


Colorectal cancer CYP2E1 Gene polymorphism Meta-analysis 



Colorectal cancer


Cytochrome P4502E1


Odds ratio


Confidence interval


Polymerase chain reaction


Restriction fragment length polymorphism


Single nucleotide polymorphisms


Hardy–Weinberg equilibrium


Conflicts of interest



  1. 1.
    Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46:765–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Sung JJ, Lau JY, Goh KL, Leung WK. Asia Pacific Working Group on Colorectal Cancer. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 2005;6:871–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Zhao P, Dai M, Chen W, et al. Cancer trends in China. Jpn J Clin Oncol. 2010;40:281–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000;343:78–85.PubMedCrossRefGoogle Scholar
  6. 6.
    Le Marchand L, Donlon T, Seifried A, Wilkens LR. Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:1019–24.PubMedGoogle Scholar
  7. 7.
    Küry S, Buecher B, Robiou-du-Pont S, et al. Combinations of cytochrome P450 gene polymorphisms enhancing the risk for sporadic colorectal cancer related to red meat consumption. Cancer Epidemiol Biomarkers Prev. 2007;16:1460–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Reszka E, Wasowicz W, Gromadzinska J. Genetic polymorphism of xenobiotic metabolising enzymes, diet and cancer susceptibility. Br J Nutr. 1996;96:609–19.Google Scholar
  9. 9.
    Cannon-Albright LA, Skolnick MH, Bishop DT, et al. Common inheritance of susceptibility to colonic adenomatous polyps and associated colorectal cancers. N Engl J Med. 1988;319:533–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Cleary SP, Cotterchio M, Shi E, Gallinger S, Harper P. Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk. Am J Epidemiol. 2010;172:1000–14.PubMedCrossRefGoogle Scholar
  11. 11.
    Guengerich FP, Kim DH, Iwasaki M. Role of human cytochrome P-450IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol. 1991;4:168–79.PubMedCrossRefGoogle Scholar
  12. 12.
    Bartsch H, Montesano R. Relevance of nitrosamines to human cancer. Carcinogenesis. 1984;5:1381–93.PubMedCrossRefGoogle Scholar
  13. 13.
    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;110:559–65.PubMedGoogle Scholar
  14. 14.
    Uematsu F, Ikawa S, Kikuchi S, et al. 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.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhou GW, Hu J, Li Q. CYP2E1 PstI/RsaI polymorphism and colorectal cancer risk: a meta-analysis. World J Gastroenterol. 2010;16:2949–53.PubMedCrossRefGoogle Scholar
  16. 16.
    Attia J, Thakkinstian A, D'Este C. Meta-analyses of molecular association studies: methodologic lessons for genetic epidemiology. J Clin Epidemiol. 2003;56:297–303.PubMedCrossRefGoogle Scholar
  17. 17.
    Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.CrossRefGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta - analyses. BMJ. 2003;327:557–60.PubMedCrossRefGoogle Scholar
  19. 19.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  20. 20.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRefGoogle Scholar
  21. 21.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRefGoogle Scholar
  22. 22.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCrossRefGoogle Scholar
  23. 23.
    Butler WJ, Ryan P, Roberts-Thomson IC. Metabolic genotypes and risk for colorectal cancer. J Gastroenterol Hepatol. 2001;16:631–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Chen K, Jin MJ, Fan CH, et al. A case–control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer. Zhonghua Liuxingbingxue Zazhi. 2005;26:659–64.PubMedGoogle Scholar
  25. 25.
    Landi S, Gemignani F, Moreno V, et al. A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer. Pharmacogenet Genomics. 2005;15:535–46.PubMedCrossRefGoogle Scholar
  26. 26.
    van der Logt EM, Bergevoet SM, Roelofs HM, et al. Role of epoxide hydrolase, NAD(P)H:quinone oxidoreductase, cytochrome P450 2E1 or alcohol dehydrogenase genotypes in susceptibility to colorectal cancer. Mutat Res. 2006;593:39–49.PubMedCrossRefGoogle Scholar
  27. 27.
    Kiss I, Orsós Z, Gombos K, et al. Association between allelic polymorphisms of metabolizing enzymes (CYP 1A1, CYP 1A2, CYP 2E1, mEH) and occurrence of colorectal cancer in Hungary. Anticancer Res. 2007;27:2931–7.PubMedGoogle Scholar
  28. 28.
    Gao CM, Takezaki T, Wu JZ, et al. CYP2E1 Rsa I polymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking. World J Gastroenterol. 2007;13:5725–30.PubMedGoogle Scholar
  29. 29.
    Cotterchio M, Boucher BA, Manno M, Gallinger S, Okey AB, Harper PA. Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:3098–107.PubMedCrossRefGoogle Scholar
  30. 30.
    Morita M, Le Marchand L, Kono S, et al. Genetic polymorphisms of CYP2E1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study. Cancer Epidemiol Biomarkers Prev. 2009;18:235–41.PubMedCrossRefGoogle Scholar
  31. 31.
    Darazy M, Balbaa M, Mugharbil A, Saeed H, Sidani H, Abdel-Razzak Z. CYP1A1, CYP2E1, and GSTM1 gene polymorphisms and susceptibility to colorectal and gastric cancer among Lebanese. Genet Test Mol Biomarkers. 2011;15:423–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Sameer AS, Nissar S, Qadri Q, Alam S, Baba SM, Siddiqi MA. Role of CYP2E1 genotypes in susceptibility to colorectal cancer in the Kashmiri population. Hum Genomics. 2011;5:530–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Silva TD, Felipe AV, Pimenta CA, Barão K, Forones NM. CYP2E1 RsaI and 96-bp insertion genetic polymorphisms associated with risk for colorectal cancer. Genet Mol Res. 2012;11:3138–45.PubMedCrossRefGoogle Scholar
  34. 34.
    Jia WH, Pan QH, Qin HD, et al. A case–control and a family-based association study revealing an association between CYP2E1 polymorphisms and nasopharyngeal carcinoma risk in Cantonese. Carcinogenesis. 2009;30:2031–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Carriere V, Berthou F, Baird S, et al. Human cytochrome P450 2E1 (CYP2E1): From genotype to phenotype. Pharmacogenetics. 1996;6:203–11.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Ou Jiang
    • 1
  • Rongxing Zhou
    • 2
  • Daoquan Wu
    • 1
  • Yu Liu
    • 1
  • Wenjian Wu
    • 1
  • Nansheng Cheng
    • 2
  1. 1.Department of Surgical OncologyThe Second People’s Hospital of NeijiangNeijiangChina
  2. 2.Department of Biliary SurgeryWest China Hospital of Sichuan UniversityChengduChina

Personalised recommendations