Debrisoquine oxidation phenotype and susceptibility to lung cancer.

Abstract

1 It has been suggested that poor metabolisers of debrisoquine are at reduced risk of developing lung cancer from smoking cigarettes. This has been investigated in 82 patients with established cancer of the lung. 2 The frequency of poor metaboliser subjects was not different from that in the normal population.3 There was no tendency for subjects with lung cancer to metabolise debrisoquine more rapidly than non-cancer subjects. 4 It is concluded that debrisoquine metabolic phenotype is not a good predictor of risk of developing lung cancer in the population at large.

The rationale for case‐control methodology in epidemiological studies of cancer risk (response to Speirs et al., 1990) [see comments]

“…The results in these studies contrast with those in the recent report of Speirs et al (1990) (Speirs et al (1990)-not specified but presumably variable and at patient discretion, others-in the morning); diet prior to debrisoquine (Speirs et al (1990)-not less than 4 h prior to last meal, others-overnight fast); medical supervision of phenotyping procedure (Speirs et al (1990)-apparently at home at patient discretion and unsupervised, othersmostly in hospital under medical supervision); concurrent medications (Speirs et or Steiner et al (1985) (71.7%).' Some years ago we reflected on the fact that the controls in this study did not apparently meet Hardy-Weinberg constraints.…”

“…The use of such a procedure is especially important when a new population is studied, a different racial group is examined, or a new laboratory or phenotyping procedure employed. In contrast to the work of Ayesh et al (1984), the lack of a control group in the Speirs et al (1990) study excludes the possibility of such a corrective analysis.…”

“…The rationale for case-control methodology in epidemiological studies of cancer risk (response to Speirs et al, 1990) A number of studies have examined the hypothesis of an association between the genetically determined ability to metabolise debrisoquine (DBR) and lung cancer susceptibility. These include Ayesh et al (1984), Caporaso et al (1988), Law et al (1989) and Roots et al (1988).…”

Lack of a relationship between the polymorphism of debrisoquine oxidation and lung cancer.

“…A bimodal distribution of the log D/HD ratio was apparent in the healthy population (Figure 1) but not in the other two groups (Figures 2 and 3). However, neither the lung cancer nor the chronic bronchitis groups showed a Gaussian distribution (Table 1) (1986) and Speirs et al (1990). Two studies (Jacqz et al, .…”

Debrisoquine oxidation phenotype and susceptibility to lung cancer [letter; comment]

“…We are responding to the criticisms of our recent article (Speirs et al, 1990) on the question of a possible association between debrisoquine oxidation phenotype and susceptibility to lung cancer made by Dr Caporaso and Professor Idle (Caporaso & Idle, 1990 (Ayesh et al, 1984;Law et al, 1989) cannot be considered as independent, as drug analysis was conducted in the same laboratory. A third study (Caporaso et al, 1988) is reported only as an abstract, and has not been subjected to peer review.…”