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A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States)

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Abstract

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1)genetic polymorphisms are involved in the activation and detoxification ofchemical carcinogens found in tobacco smoke; thus they may influence hostsusceptibility to lung cancer. In this study at Massachusetts GeneralHospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) weevaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms andlung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspIheterozygous genotype was present in 18 percent of cases and 16 percent ofcontrols, and one percent of cases and controls were CYP1A1 MspI homozygousvariant. The GSTM1 null genotype was detected in 54 percent of cases and 52percent of controls. After adjusting for age, gender, pack-years of smoking,and years since quitting smoking, while neither the CYP1A1 MspI heterozygousgenotype alone nor the GSTM1 null genotype alone were associated with asignificant increas e in lung cancer risk, having both genetic traits wasassociated with a twofold increase in risk (95 percent confidence interval[CI] = 1.0-3.4). Our data did not provide enough evidence for a substantialmodification of the effect of pack-years on lung cancer risk by the CYP1A1MspI and GSTM1 genotypes. However, limitations of our study preclude aconclusion about this potential interaction.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA

    Montserrat García-Closas

  2. Department of Environmental Health, Occupational Health Program, Harvard School of Public Health, Boston, USA

    Karl T. Kelsey, Xiping Xu & David C. Christiani

  3. Department of Cancer Biology, Harvard School of Public Health, Boston, USA

    Karl T. Kelsey

  4. Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, USA

    John K. Wiencke

  5. Thoracic Surgery Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    John C. Wain

  6. Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    David C. Christiani

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  1. Montserrat García-Closas
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García-Closas, M., Kelsey, K.T., Wiencke, J.K. et al. A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States). Cancer Causes Control 8, 544–553 (1997). https://doi.org/10.1023/A:1018481910663

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