Molecular Biology Reports

, Volume 39, Issue 4, pp 3533–3540

Association between CYP1A1 polymorphism and colorectal cancer risk: a meta-analysis



Colorectal cancer is one of the most common forms of cancer and is the third leading cause of cancer-related death worldwide. Published data on the association between CYP1A1 (MspI and Ile462Val) polymorphisms and colorectal cancer risk are inconclusive. To address these issues, we carried out a meta-analysis of available case–control study. Online electronic searches of PubMed were performed. We identified 17 studies (6,673 colorectal cancer patients and 8,102 control subjects) that examined the association between CYP1A1 (MspI and Ile462Val) polymorphisms and risk of colorectal cancer. For CYP1A1 MspI polymorphism, we performed a meta-analysis from 13 studies including 5,468 cases and 6,492 controls. Overall, there was no statistically significant association between CYP1A1 MspI polymorphism and colorectal cancer susceptibility. In the subgroup analyses based on ethnicities, no statistically significant associations were observed in all genetic models. With respect to CYP1A1 Ile462Val polymorphism, a total of 14 studies including 6,654 cases and 7,859 controls were involved in this meta-analysis. The CYP1A1 Ile462Val polymorphism was associated with risk of colorectal cancer. Ethnic subgroup analyses revealed that significant associations were found in Asians and Caucasians. In summary, this meta-analysis suggests that CYP1A1 Ile462Val polymorphism was a low-penetrance susceptibility gene in colorectal cancer development. On the contrary, CYP1A1 MspI polymorphism does not seem capable of modifying colorectal cancer risk.


CYP1A1 polymorphism Colorectal cancer Meta-analysis 


  1. 1.
    Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA Cancer J Clin 60:277–300. doi:10.3322/caac.20073 PubMedCrossRefGoogle Scholar
  2. 2.
    Weitz J, Koch M, Debus J, Hohler T, Galle PR et al (2005) Colorectal cancer. Lancet 365:153–165. doi:10.1016/S0140-6736(05)17706-X PubMedCrossRefGoogle Scholar
  3. 3.
    Walther A, Johnstone E, Swanton C, Midgley R, Tomlinson I et al (2009) Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer 9:489–499. doi:10.1038/nrc2645 PubMedCrossRefGoogle Scholar
  4. 4.
    de la Chapelle A (2004) Genetic predisposition to colorectal cancer. Nat Rev Cancer 4:769–780. doi:10.1038/nrc1453 PubMedCrossRefGoogle Scholar
  5. 5.
    Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J et al (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343:78–85. doi:10.1056/NEJM200007133430201 PubMedCrossRefGoogle Scholar
  6. 6.
    Cleary SP, Cotterchio M, Shi E, Gallinger S, Harper P (2010) Cigarette smoking, genetic variants in carcinogen-metabolizing enzymes, and colorectal cancer risk. Am J Epidemiol 172:1000–1014. doi:10.1093/aje/kwq245 PubMedCrossRefGoogle Scholar
  7. 7.
    Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G et al (2010) SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res 38:D237–D243. doi:10.1093/nar/gkp970 PubMedCrossRefGoogle Scholar
  8. 8.
    Nebert DW, Russell DW (2002) Clinical importance of the cytochromes P450. Lancet 360:1155–1162. doi:10.1016/S0140-6736(02)11203-7 PubMedCrossRefGoogle Scholar
  9. 9.
    Nebert DW, Dalton TP (2006) The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer 6:947–960. doi:10.1038/nrc2015 PubMedCrossRefGoogle Scholar
  10. 10.
    Wrensch MR, Miike R, Sison JD, Kelsey KT, Liu M et al (2005) CYP1A1 variants and smoking-related lung cancer in San Francisco Bay area Latinos and African Americans. Int J Cancer 113:141–147. doi:10.1002/ijc.20537 PubMedCrossRefGoogle Scholar
  11. 11.
    Sivaraman L, Leatham MP, Yee J, Wilkens LR, Lau AF et al (1994) CYP1A1 genetic polymorphisms and in situ colorectal cancer. Cancer Res 54:3692–3695PubMedGoogle Scholar
  12. 12.
    Landi S, Gemignani F, Moreno V, Gioia-Patricola L, Chabrier A et al (2005) A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer. Pharmacogenet Genomics 15:535–546PubMedCrossRefGoogle Scholar
  13. 13.
    Hayashi S, Watanabe J, Kawajiri K (1992) High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu-class glutathione S-transferase genes. Jpn J Cancer Res 83:866–870PubMedCrossRefGoogle Scholar
  14. 14.
    Ravnik-Glavac M, Dolzan V, Breskvar K (1998) Genetic polymorphisms of xenobiotic metabolizing enzymes in human colorectal cancer. Radiol Oncol 32:35–39Google Scholar
  15. 15.
    Fritsche E, Bruning T, Jonkmanns C, Ko Y, Bolt HM et al (1999) Detection of cytochrome P450 1B1 Bfr I polymorphism: genotype distribution in healthy German individuals and in patients with colorectal carcinoma. Pharmacogenetics 9:405–408PubMedCrossRefGoogle Scholar
  16. 16.
    Ishibe N, Stampfer M, Hunter DJ, Hennekens C, Kelsey KT (2000) A prospective study of cytochrome P450 1A1 polymorphisms and colorectal cancer risk in men. Cancer Epidemiol Biomarkers Prev 9:855–856PubMedGoogle Scholar
  17. 17.
    Sachse C, Smith G, Wilkie MJ, Barrett JH, Waxman R et al (2002) A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis 23:1839–1849PubMedCrossRefGoogle Scholar
  18. 18.
    Ye Z, Parry JM (2002) Genetic polymorphisms in the cytochrome P450 1A1, glutathione S-transferase M1 and T1, and susceptibility to colon cancer. Teratog Carcinog Mutagen 22:385–392. doi:10.1002/tcm.10035 PubMedCrossRefGoogle Scholar
  19. 19.
    Slattery ML, Samowtiz W, Ma K, Murtaugh M, Sweeney C et al (2004) CYP1A1, cigarette smoking, and colon and rectal cancer. Am J Epidemiol 160:842–852. doi:10.1093/aje/kwh298 PubMedCrossRefGoogle Scholar
  20. 20.
    Chen K, Jin MJ, Fan CH, Song L, Jiang QT et al (2005) A case-control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer. Zhonghua Liu Xing Bing Xue Za Zhi 26:659–664PubMedGoogle Scholar
  21. 21.
    Little J, Sharp L, Masson LF, Brockton NT, Cotton SC et al (2006) Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: a case-control study in the Grampian region of Scotland. Int J Cancer 119:2155–2164. doi:10.1002/ijc.22093 PubMedCrossRefGoogle Scholar
  22. 22.
    Kiss I, Orsos Z, Gombos K, Bogner B, Csejtei A et al (2007) Association between allelic polymorphisms of metabolizing enzymes (CYP 1A1, CYP 1A2, CYP 2E1, mEH) and occurrence of colorectal cancer in Hungary. Anticancer Res 27:2931–2937PubMedGoogle Scholar
  23. 23.
    Yeh CC, Sung FC, Tang R, Chang-Chieh CR, Hsieh LL (2007) Association between polymorphisms of biotransformation and DNA-repair genes and risk of colorectal cancer in Taiwan. J Biomed Sci 14:183–193. doi:10.1007/s11373-006-9139-x PubMedCrossRefGoogle Scholar
  24. 24.
    Yoshida K, Osawa K, Kasahara M, Miyaishi A, Nakanishi K et al (2007) Association of CYP1A1, CYP1A2, GSTM1 and NAT2 gene polymorphisms with colorectal cancer and smoking. Asian Pac J Cancer Prev 8:438–444PubMedGoogle Scholar
  25. 25.
    Kobayashi M, Otani T, Iwasaki M, Natsukawa S, Shaura K et al (2009) Association between dietary heterocyclic amine levels, genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of colorectal cancer: a hospital-based case-control study in Japan. Scand J Gastroenterol 44:952–959. doi:10.1080/00365520902964721 PubMedCrossRefGoogle Scholar
  26. 26.
    Nisa H, Kono S, Yin G, Toyomura K, Nagano J et al (2010) Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. BMC Cancer 10:274. doi:10.1186/1471-2407-10-274 PubMedCrossRefGoogle Scholar
  27. 27.
    Rohlfs RV, Weir BS (2008) Distributions of Hardy–Weinberg equilibrium test statistics. Genetics 180:1609–1616. doi:10.1534/genetics.108.088005 PubMedCrossRefGoogle Scholar
  28. 28.
    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558. doi:10.1002/sim.1186 PubMedCrossRefGoogle Scholar
  29. 29.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  30. 30.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  31. 31.
    Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8:15–17Google Scholar
  32. 32.
    Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24:1291–1306. doi:10.1002/sim.2010 PubMedCrossRefGoogle Scholar
  33. 33.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRefGoogle Scholar
  34. 34.
    Sergentanis TN, Economopoulos KP (2010) Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a meta-analysis. Breast Cancer Res Treat 122:459–469. doi:10.1007/s10549-009-0694-5 PubMedCrossRefGoogle Scholar
  35. 35.
    Jin JQ, Hu YY, Niu YM, Yang GL, Wu YY et al (2011) CYP1A1 Ile462Val polymorphism contributes to colorectal cancer risk: a meta-analysis. World J Gastroenterol 17:260–266PubMedCrossRefGoogle Scholar
  36. 36.
    Masson LF, Sharp L, Cotton SC, Little J (2005) Cytochrome P-450 1A1 gene polymorphisms and risk of breast cancer: a HuGE review. Am J Epidemiol 161:901–915. doi:10.1093/aje/kwi121 PubMedCrossRefGoogle Scholar
  37. 37.
    Quinones L, Lucas D, Godoy J, Caceres D, Berthou F et al (2001) CYP1A1, CYP2E1 and GSTM1 genetic polymorphisms. The effect of single and combined genotypes on lung cancer susceptibility in Chilean people. Cancer Lett 174:35–44PubMedCrossRefGoogle Scholar
  38. 38.
    Hirschhorn JN, Lohmueller K, Byrne E, Hirschhorn K (2002) A comprehensive review of genetic association studies. Genet Med 4:45–61PubMedCrossRefGoogle Scholar
  39. 39.
    Kaklamani VG, Hou N, Bian Y, Reich J, Offit K et al (2003) TGFBR1*6A and cancer risk: a meta-analysis of seven case-control studies. J Clin Oncol 21:3236–3243. doi:10.1200/JCO.2003.11.524 PubMedCrossRefGoogle Scholar
  40. 40.
    Moghaddam AA, Woodward M, Huxley R (2007) Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev 16:2533–2547. doi:10.1158/1055-9965.EPI-07-0708 PubMedCrossRefGoogle Scholar
  41. 41.
    Boland CR (2010) Chronic inflammation, colorectal cancer and gene polymorphisms. Dig Dis 28:590–595. doi:10.1159/000320053 PubMedCrossRefGoogle Scholar
  42. 42.
    Din FV, Theodoratou E, Farrington SM, Tenesa A, Barnetson RA et al (2010) Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut 59:1670–1679. doi:10.1136/gut.2009.203000 PubMedCrossRefGoogle Scholar
  43. 43.
    Rheem DS, Baylink DJ, Olafsson S, Jackson CS, Walter MH (2010) Prevention of colorectal cancer with vitamin D. Scand J Gastroenterol 45:775–784. doi:10.3109/00365521003734125 PubMedCrossRefGoogle Scholar
  44. 44.
    Arain MA, Abdul Qadeer A (2010) Systematic review on “vitamin E and prevention of colorectal cancer”. Pak J Pharm Sci 23:125–130PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Yuan Zheng
    • 1
  • Jing-Jun Wang
    • 1
  • Liang Sun
    • 2
  • Hong-Lei Li
    • 1
  1. 1.Department of Center for Disease Control and Prevention of Shaanxi ProvinceXi’anPeople’s Republic of China
  2. 2.Department of Center for Disease Control and Prevention of FuyangFuyangChina

Personalised recommendations