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Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma

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Abstract

The effect of genetic polymorphisms for glutathione S-transferase ( GST) M1, GSTT1, GSTP1-1 ( GSTP1), cytochrome P450 2E1 ( CYP2E1) and aldehyde dehydrogenase 2 ( ALDH2) on the risk of hepatocellular carcinoma (HCC) was observed in 78 Japanese patients with HCC and 138 non-cancer hospital controls. We found a positive association between cumulative amounts of alcohol consumption (≧600,000 ml in a lifetime) and the risk of HCC (OR=4.52, 95% CI 2.39–8.55). However, cigarette smoking was not significantly related to the risk of HCC (OR=1.23, 95% CI 0.57–2.68). The allelic frequencies of GSTM1, GSTT1, GSTP1, CYP2E1and ALDH2of HCC patients were not significantly different from those of controls when odds ratios were only adjusted for age and gender except for any 2 alleles of ALDH2in drinkers (OR=2.53, 95% CI 1.21–5.31). However, the frequency of any C2alleles of CYP2E1 and any 2 alleles of ALDH2were significantly higher than those of controls (OR=5.77, 95% CI 1.24–27.39, OR=9.77, 95% CI 1.63–58.60) when covariates including viremia were selected by using stepwise logistic regression analysis. We conclude that habitual alcohol drinking is likely to lead to an increased risk of HCC, and any C2alleles of CYP2E1as well as any two alleles of ALDH2were also associated with an increased risk of HCC.

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Acknowledgements

This work was supported in part by a grant-in-aid from the Ministry of Education, Science and Culture of Japan and a grant-in-aid from the Ministry of Welfare and Labor of Japan.

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Authors and Affiliations

  1. Nissan Motor Health Insurance Society, Nissan Motor Car Co. Ltd., Kyushu Plant, Fukuoka, Japan

    Masahiro Munaka

  2. Department of Neurosurgery, School of Medicine, University Hospital, Kitakyushu, Japan

    Kiyotaka Kohshi

  3. Division of Hyperbaric Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Kiyotaka Kohshi

  4. Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Toshihiro Kawamoto

  5. Department of First Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Shin Takasawa, Naoki Nagata & Hideaki Itoh

  6. Divison of Health Care and Promotion Occupational Health Training Center, University of Occupational and Environmental Health, Kitakyushu, Japan

    Susumu Oda

  7. Department of Public Health, Miyazaki Medical College, 5200 Kihara, Kiyotake, 889-1692, Miyazaki, Japan

    Takahiko Katoh

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  1. Masahiro Munaka
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  8. Takahiko Katoh
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Correspondence to Takahiko Katoh.

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Munaka, M., Kohshi, K., Kawamoto, T. et al. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma. J Cancer Res Clin Oncol 129, 355–360 (2003). https://doi.org/10.1007/s00432-003-0439-5

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  • DOI: https://doi.org/10.1007/s00432-003-0439-5

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