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Epidemiology

Polymorphisms of the CYP1A1 and Glutathione S-Transferase Genes Associated with Susceptibility to Lung Cancer in Relation to Cigarette Dose in a Japanese Population

Kei Nakachi, Kazue Imai, Shin-ichi Hayashi and Kaname Kawajiri
Kei Nakachi
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Kazue Imai
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Shin-ichi Hayashi
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Kaname Kawajiri
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DOI:  Published July 1993
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Abstract

An association of lung cancer susceptibility with an MspI restriction site polymorphism of the CYP1A1 gene was reported in our previous study. This polymorphism has been subsequently found to be closely linked to another isoleucine-valine (Ile-Val) polymorphism, which resulted in an Ile-Val amino acid replacement in the heme-binding region of P4501A1.

We report here that genetic risk for squamous cell carcinoma of the lung was associated with these two polymorphisms of the CYP1A1 gene in terms of genotype frequencies and cigarette-smoking dose and that a more increased risk was observed for the individuals with “susceptible” genotypes of CYP1A1 combined with a deficient genotype of a µ-class glutathione S-transferase (GST1), which detoxifies the electrophilic metabolites of aromatic hydrocarbon procarcinogens activated by P4501A1. We first compared the total amounts of cigarettes consumed during a lifetime among 85 patients with squamous cell carcinoma of the lung, whose CYP1A1 and GST1 genes were identified. The patients with a susceptible homozygote of each of the MspI and Ile-Val polymorphisms contracted the carcinoma after smoking fewer cigarettes than those with other genotypes. When the GST1 polymorphism was taken into account, the cumulative cigarette amounts in combined genotyping of the two genes showed distinct differences, resulting in the lowest cigarette dose observed for the patients with a susceptible MspI or Ile-Val genotype of CYP1A1 combined with a deficient GST1 homozygote. Next, a case-control study revealed that the individuals with the susceptible MspI or Ile-Val genotype combined with deficient GST1 were at remarkably high risk with an odds ratio of 16.00 or 41.00, respectively (95% confidence interval, 3.76–68.02 or 8.68–193.61, respectively), at a low dose level of cigarette smoking.

Footnotes

  • ↵1 Supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture and the Ministry of Health and Welfare of Japan and a Grant-in-Aid from the Ministry of Health and Welfare for the Comprehensive 10-Year Strategy for Cancer Control, Japan.

  • ↵2 To whom requests for reprints should be addressed, at Department of Epidemiology, Saitama Cancer Center Research Institute, 818 Komuro, Ina. Saitama 362, Japan.

  • Received February 1, 1993.
  • Accepted April 27, 1993.
  • ©1993 American Association for Cancer Research.
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July 1993
Volume 53, Issue 13
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Polymorphisms of the CYP1A1 and Glutathione S-Transferase Genes Associated with Susceptibility to Lung Cancer in Relation to Cigarette Dose in a Japanese Population
Kei Nakachi, Kazue Imai, Shin-ichi Hayashi and Kaname Kawajiri
Cancer Res July 1 1993 (53) (13) 2994-2999;

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Polymorphisms of the CYP1A1 and Glutathione S-Transferase Genes Associated with Susceptibility to Lung Cancer in Relation to Cigarette Dose in a Japanese Population
Kei Nakachi, Kazue Imai, Shin-ichi Hayashi and Kaname Kawajiri
Cancer Res July 1 1993 (53) (13) 2994-2999;
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