Lung cancer and the debrisoquine metabolic phenotype

Our plain-English summary of Lung cancer and the debrisoquine metabolic phenotype, by N.E. Caporaso, M.A. Tucker, R.N. Hoover, et al (Journal of the National Cancer Institute, 1990).

The study

• Authors: N.E. Caporaso, M.A. Tucker, R.N. Hoover, R.B. Hayes, L.W. Pickle, H.J. Issaq, G.M. Muschik, L. Green-Gallo, D. Buivys, S. Aisner
• Journal: Journal of the National Cancer Institute
• Published: 1990;82(15):1264-72
• Cited by: 178 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In a case-control study, we tested the hypothesis that the genetically determined ability to metabolize debrisoquine is related to risk of lung cancer. Overall, individuals who were extensive metabolizers of debrisoquine were at significantly greater risk of lung cancer than those who were poor or intermediate metabolizers (odds ratio = 6.1; 95% confidence interval = 2.2-17.1). In this study, case patients had lung cancer, and control subjects had either chronic obstructive pulmonary disease or cancers other than lung cancer. Results were adjusted for age, race, asbestos exposure, and smoking. Both black and white individuals who were extensive metabolizers of debrisoquine were at significantly increased risk after similar adjustment (for blacks, odds ratio = 4.5, 95% confidence interval = 1.1-18.1; for whites, odds ratio = 10.2, 95% confidence interval = 2.0-51.4). Significantly increased risk of lung cancer was also present for individuals who were extensive metabolizers when subjects with chronic obstructive pulmonary disease or other cancers were considered separately. These data confirm that the ability to metabolize debrisoquine is a major determinant of susceptibility to lung cancer. Evaluation of the marker in other case-control settings, further exploration of racial differences, and the prospective evaluation of this marker in subgroups at high risk of lung cancer are areas worthy of further study.

In plain English

This case-control study, at the University of Maryland Hospital and the Baltimore Veterans Administration Hospital from 1985 to 1989, tested whether an inherited ability to break down the drug debrisoquine was related to lung cancer risk. It compared 96 lung cancer patients with 92 controls: 55 with chronic obstructive pulmonary disease and 37 with other cancers. Each took a small debrisoquine test dose, and urine tests sorted them into extensive, intermediate or poor metabolizers. Adjusted for age, race, smoking and a yes-or-no history of occupational asbestos exposure, extensive metabolizers had a relative risk of lung cancer of 6.1 (95% confidence interval 2.2-17.1) versus poor and intermediate metabolizers combined. No asbestos fiber type was named. For black subjects the adjusted odds ratio was 4.5 (95% confidence interval 1.1-18.1); for white subjects, 10.2 (2.0-51.4). About 40% of lung cancer patients and lung-disease controls reported asbestos exposure, versus 14% of other-cancer controls. The authors concluded that extensive metabolizers had a sixfold increased risk. They noted that only 26% of potentially eligible subjects were enrolled and that a case-control design cannot prove cause.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Hospital-based case-control study with two separate control groups
• Who was studied: 96 lung cancer cases and 92 controls (55 with chronic obstructive pulmonary disease, 37 with other cancers), from the University of Maryland Hospital and the Baltimore Veterans Administration Hospital, July 1985 to March 1989; nearly all cases were men
• Exposure: The main factor studied was the genetically determined debrisoquine metabolic phenotype, measured after a 10-mg oral tracer dose. Occupational asbestos exposure (yes or no, no fiber type given) was one of the factors the results were adjusted for.
• Main results:
  • After adjustment, extensive metabolizers had a relative risk of lung cancer of 6.1 (95% confidence interval 2.2-17.1) compared with poor and intermediate metabolizers combined. The crude estimate was 5.9 (95% confidence interval 2.1-16.3).
  • Adjusted odds ratio for extensive metabolizers among black subjects was 4.5 (95% CI 1.1-18.1) and among white subjects 10.2 (95% CI 2.0-51.4), as printed in the article's abstract. Table 2 prints these intervals as 1.1-18.0 and 2.0-51.5.
  • The risk was elevated against each control group separately: 6.0 (95% CI 2.0-17.9) versus chronic obstructive pulmonary disease controls, and 10.4 (95% CI 2.0-40.3) versus other-cancer controls
  • Among cases, 1 was a poor metabolizer and 4 were intermediate metabolizers. Among controls, 12 were poor and 12 were intermediate metabolizers.
  • About 40% of lung cancer cases and of chronic obstructive pulmonary disease controls reported occupational asbestos exposure, compared with 14% of other-cancer controls
  • Lung cancer patients with adenocarcinoma had a higher natural log metabolic ratio (0.27) than those with other tumor types (-0.17). The difference (P = .06) fell just short of statistical significance.
• The authors' conclusion: The authors concluded that extensive metabolizers of debrisoquine were at a sixfold increased risk of lung cancer compared with poor and intermediate metabolizers. They called for further study in other settings and in prospective studies.
• Limitations the authors state:
  • A high number of exclusions: only 26% of potentially eligible subjects were ultimately enrolled
  • The metabolic ratio cannot perfectly assign the genotype, so some misclassification is possible
  • The case-control design cannot show whether the association is a cause or an effect of the tumor, and cannot directly prove a causal relation

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Case-Control Study, Odds Ratio, confidence interval, Asbestos Exposure.

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