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

  • Masahiro Munaka
  • Kiyotaka Kohshi
  • Toshihiro Kawamoto
  • Shin Takasawa
  • Naoki Nagata
  • Hideaki Itoh
  • Susumu Oda
  • Takahiko Katoh
Original Paper


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.


Genetic polymorphism GSTM1 CYP2E1 ALDH2 Hepatocellular carcinoma 



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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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Masahiro Munaka
    • 1
  • Kiyotaka Kohshi
    • 2
    • 3
  • Toshihiro Kawamoto
    • 4
  • Shin Takasawa
    • 5
  • Naoki Nagata
    • 5
  • Hideaki Itoh
    • 5
  • Susumu Oda
    • 6
  • Takahiko Katoh
    • 7
  1. 1.Nissan Motor Health Insurance SocietyNissan Motor Car Co. Ltd., Kyushu PlantFukuokaJapan
  2. 2.Department of NeurosurgerySchool of Medicine, University HospitalKitakyushuJapan
  3. 3.Division of Hyperbaric Medicine, School of Medicine University of Occupational and Environmental HealthKitakyushuJapan
  4. 4.Department of Environmental Health, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan
  5. 5.Department of First Surgery, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan
  6. 6.Divison of Health Care and Promotion Occupational Health Training CenterUniversity of Occupational and Environmental HealthKitakyushuJapan
  7. 7.Department of Public HealthMiyazaki Medical CollegeMiyazakiJapan

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