Summary
Cigarette smoking has been associated with increased risk of hepatocellular carcinoma (HCC) in some epidemiological studies. Cytochrome P450 1A1 (CYP1A1) is involved in the biotransformation of tobacco-derived polycyclic aromatic hydrocarbons (PAHs) into carcinogenic metabolites. The aim of this study was to determine whether CYP1A1 polymorphisms were related to HCC risk among chronic hepatitis B virus (HBV) carriers. Genotypic variants of CYP1A1 were determined using polymerase chain reaction in 81 incident cases of HCC and 409 controls nested in a cohort study of 4841 male chronic HBV carriers. No overall association between CYP1A1 genotypes and HCC was observed. The presence of the MspI (odds ratio (OR) 3.15, P= 0.0196) or Ile-Val (OR 1.99, P= 0.0855) variant allele of CYP1A1 increased HCC risk among smokers, but posed no increased risk among non-smokers. The smoking-related HCC risk was most pronounced among those who had a susceptible allele of the CYP1A1 and a deficient genotype of glutathione S-transferase M1, which detoxifies PAH electrophilic metabolites produced by CYP1A1. In the absence of the Ile-Val variant allele, the MspI polymorphism was still associated with smoking-related HCC. This study suggests that tobacco-derived PAHs play a role in HCC risk among chronic HBV carriers, and CYP1A1 polymorphism is an important modulator of the hepatocarcinogenic effect of PAHs. The MspI and Ile-Val polymorphisms of CYP1A1 may have different mechanisms for increasing susceptibility to smoking-related HCC.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Agundez, J. A. G., Olivera, M., Ladero, J. M., Rodriguez-Lescure, A., Ledesma, M. C., Diaz-Rubio, M., Meyer, U. A. & Benitez, J. (1996). Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers. Pharmacogenetics 6: 501–512.
Beasley, R. P. (1988). Hepatitis B virus: the major etiology of hepatocellular carcinoma. Cancer 61: 1942–1956.
Chen, C. J., Liang, K. Y., Chang, A. S., Chang, Y. C., Lu, S. N., Liaw, Y. F., Chang, W. Y., Sheen, M. C. & Lin, T. M. (1991). Effects of hepatitis B virus, alcohol drinking, cigarette smoking and familial tendency on hepatocellular carcinoma. Hepatology 13: 398–406.
Chen, C. J., Yu, M. W., Liaw, Y. F., Wang, L. W., Chiamprasert, S., Matin, F., Hirvonen, A., Bell, D. A. & Santella, R. M. (1996). Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma. Am J Hum Genet 59: 128–134.
Crofts, F., Taioli, E., Trachman, J., Cosma, G. N., Currie, D., Toniolo, P. & Garte, S. J. (1994). Functional significance of different human CYP1A1 genotypes. Carcinogenesis 15: 2961–2963.
Gallagher, E. P., Wienkers, L. C., Stapleton, P. L., Kunze, K. L. & Eaton, D. L. (1994). Role of human microsomal and human complementary DNA-expressed cytochrome P4501A2 and P4503A4 in the bioactivation of aflatoxin B1 . Cancer Res 54: 101–108.
Guengerich, F. P. (1991). Interindividual variation in biotransformation of carcinogens: basis and relevance. In Molecular Dosimetry and Human Cancer: Analytical, Epidemiological, and Social Considerations, Groopman JD and Skipper PL (eds), pp. 27–51. CRC Press: Boston
Guengerich, F. P. & Shimada, T. (1991). Oxidation of toxic and carcinogenic chemicals by human cytochrome P450 enzymes. Chem Res Toxicol 4: 391–407.
Hein, D. W., Doll, M. A., Rustan, T. D., Gray, K., Feng, Y., Ferguson, R. J. & Grant, D. M. (1993). Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 14: 1633–1638.
International Agency for Research on Cancer (1986). IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Vol 38, Tobacco Smoking. IARC: Lyon
Kawajiri, K., Nakachi, K., Imai, K., Watanabe, J. & Hayashi, S. (1993). The CYP1A1 gene and cancer susceptibility. Crit Rev Oncol Hematol 14: 77–87.
Mannervik, B. & Danielson, U. H. (1988). Glutathione transferase: structure and catalytic activity. Crit Rev Biochem Mol Biol 23: 281–337.
McKinnon, R. A., Hall, P. M., Quattrochi, L. C., Tukey, R. H. & McManus, M. E. (1991). Localization of CYP1A1 and CYP1A2 messenger RNA in normal human liver and in hepatocellular carcinoma by in situ hybridization. Hepatology 14: 848–856.
Muscat, J. E., Richie, J. P. Jr, Thompson, S. & Wynder, E. L. (1996). Gender differences in smoking and risk for oral cancer. Cancer Res 56: 5192–5197.
Nakachi, K., Imai, K., Hayashi, S. & Kawajiri, K. (1993). Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res 53: 2994–2999.
Oyama, T., Mitsudomi, T., Kawamoto, T., Ogami, A., Osaki, T., Kodama, Y. & Yasumoto, K. (1995). Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese. In Arch Occup Environ Health 67: 253–256.
Petersen, D. D., McKinney, C. E., Lkeya, K., Smith, H. H., Bale, A. E., McBride, O. W. & Nebert, D. W. (1991). Human CYP1A1 gene: cosegregation of the enzyme inducibility phenotype and an RFLP. Am J Hum Genet 48: 720–725.
Rebbeck, T. R. (1997). Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiol Biomarkers Prev 6: 733–743.
Schweikl, H., Taylor, J. A., Kitareewan, S., Linko, P., Nagorney, D. & Goldstein, J. A. (1993). Expression of CYP1A1 and CYP1A2 genes in human liver. Pharmacogenetics 3: 239–249.
Shen, F. M., Lee, M. K., Gong, H. M., Cai, X. Q. & King, M. C. (1991). Complex segregation analysis of primary hepatocellular carcinoma in Chinese families: interaction of inherited susceptibility and hepatitis B viral infection. Am J Hum Genet 49: 88–93.
Shimada, T., Yun, C. H., Yamazaki, H., Gautier, J. C., Beaune, P. H. & Guengerich, F. P. (1992). Characterization of human lung microsomal cytochrome P450 1A1 and its role in oxidation of chemical carcinogens. Mol Pharmacol 41: 856–864.
Sivaraman, L., Leatham, M. P., Yee, J., Wilkens, L. R., Lau, A. F. & Marchand, L. L. (1994). CYP1A1 genetic polymorphisms and in situ colorectal cancer. Cancer Res 54: 3692–3695.
Spitz, M. R., Fueger, J. J., Beddingfield, N. A., Annegers, J. F., Hsu, T. C. & Newell, G. R. (1989). Chromosome sensitivity to bleomycin-induced mutagenesis, an independent risk factor for upper aerodigestive tract cancers. Cancer Res 49: 4626–4628.
Talaska, G., Al-Juburi, AZSS & Kadlubar, F. F. (1991). Smoking related carcinogen-DNA adducts in biopsy samples of human urinary bladder: identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct. Proc Natl Acad Sci USA 88: 5350–5354.
Tiollais, P., Pourcel, C. & Dejean, A. (1985). The hepatitis B virus. Nature 317: 489–495.
Tsukuma, H., Hiyama, T., Oshima, A., Sobue, T., Fujimoto, I., Kasugai, H., Kojima, J., Sasaki, Y., Imaoka, S., Horiuchi, N. & Okuda, S. (1990). A case-control study of hepatocellular carcinoma in Osaka, Japan. Int J Cancer 45: 231–236.
Wynder, E. L. & Hoffmann, D. (1994). Smoking and lung cancer: scientific challenges and opportunities. Cancer Res 54: 5284–5295.
Yu, M. C., Tong, M. J., Govindarajan, S. & Henderson, B. E. (1991). Nonviral risk factors for hepatocellular carcinoma in a low-risk population, the Non-Asians of Los Angeles County, California. J Natl Cancer Inst 83: 1820–1826.
Yu, M. W., You, S. L., Chang, A. S., Lu, S. N., Liaw, Y. F. & Chen, C. J. (1991). Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan. Cancer Res 51: 5621–5625.
Yu, M. W. & Chen, C. J. (1994). Hepatitis B and C viruses in the development of hepatocellular carcinoma. Crit Rev Oncol Hematol 17: 71–91.
Yu, M. W., Gladek-Yarborough, A., Chiamprasert, S., Santella, R. M., Liaw, Y. F. & Chen, C. J. (1995a). Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma. Gastroenterology 109: 1266–1273.
Yu, M. W., Hsieh, H. H., Pan, W. H., Yang, C. S. & Chen, C. J. (1995b). Vegetable consumption, serum retinol level, and risk of hepatocellular carcinoma. Cancer Res 55: 1301–1305.
Yu, M. W., Lien, J. P., Santella, R. M., Liaw, Y. F. & Chen, C. J. (1997). Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular carcinoma among chronic hepatitis B carriers in Taiwan. J Hepatol 27: 320–330.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Yu, MW., Chiu, YH., Yang, SY. et al. Cytochrome P450 1A1 genetic polymorphisms and risk of hepatocellular carcinoma among chronic hepatitis B carriers. Br J Cancer 80, 598–603 (1999). https://doi.org/10.1038/sj.bjc.6690397
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690397
Keywords
This article is cited by
-
Are CYP1A1 polymorphisms associated with the risk of hepatocellular carcinoma?
Molecular Biology Reports (2013)
-
Interactions between CYP1A1 polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies
Molecular Biology Reports (2012)
-
Identification of CYP2C9*2 Allele in HepG2 Cell Line
International Journal of Gastrointestinal Cancer (2006)