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Since my original publication in 1995 reporting high rates of denial
of smoking in Japanese women,1 and Prof Yano's alternative assessment of
the evidence,2 there has been an ongoing correspondence between the two of
us.3-6 In his latest letter6 Yano asks whether my paper1 should have been
published because it suffers from "erroneous interpretations based on
My calculations critically depe...
My calculations critically depended on the detection of high urinary
cotinine/creatinine ratios (CCR) of >100 ng/mg in 28 women who reported
that they were nonsmokers. Yano argues that the CCR measurement may have
been unreliable because the dry ice sent with the urine samples had
sublimated before it reached the laboratory (a problem I have no record or
memory of), and that, if the sample had been exposed to high temperature,
the measurement might have been inaccurate. Although other references7,8
argue that cotinine levels in unfrozen samples are reliable for research
purposes, Yano cites the results of one study9 which did show some
increase in cotinine levels in samples stored at high temperatures.
However, even at the highest temperature (60°C) and longest storage time
(30 days) tested, the increase was by less than 2-fold. In contrast, in
25 of the 28 women reclassified as current smokers, their CCR was more
than 2-fold above the, conservative, 100 ng/mg cut-off used, and in 23 of
them the CCR was over 500 ng/mg. I do not consider this doubt about
possible exposure of samples to high temperature is relevant. If Yano
thought it was, why was it not mentioned in his paper?2 I note that Yano
states that the potential problem only applied to the first batch of
samples. If so, it would be relevant to compare the results for the two
batches. My database does not have details of batch. Does Yano's?
Using 100 ng/ml as indicative of true smoking, I estimated that 28/98
= 29% of true smokers denied smoking. In contrast 8/298 = 2.7% of true
nonsmokers could be reclassified as smokers. The former misclassification
rate, which can cause
substantial bias to estimates of lung cancer risk in nonsmokers
associated with spousal smoking, is much higher than the reverse
misclassification rate, which in any case has a much lower biasing
The calculations in Yano's latest letter6 are off the point as they
are based on the assumption that self reported smoking is 100% accurate
and that it is CCR which is subject to error. The whole point of the
study was to test the accuracy of self report using CCR as the gold
standard. Clearly CCR is not 100% accurate, but Yano gives no reason why
such inaccuracy should affect the major conclusion of my paper.1
Yano is concerned that my formula depends on the prevalence of
smoking. I am not sure why. One is attempting to answer the question
"What proportion of true smokers deny smoking?" and clearly the number of
true smokers must be the denominator in the calculation.
Yano states that Proctor "finally understood and accepted my point on
the misclassification formula," but that was before he had consulted me
and realized that Yano's approach was erroneous. Then, as now, my views
and Yano's seem irreconcilable, and as it was not possible to prepare a
paper satisfactory to all, I was asked by Proctor to prepare a paper under
my name. Clearly the situation is not ideal, but at least the data and
the differing interpretations are in the literature for scientists to form
their own judgement. I retain my view that my interpretation is correct
and that the measurements made are valid enough for the conclusions I
Peter N Lee
P.N. Lee Statistics and Computing Ltd.,
17 Cedar Road,
Sutton, Surrey, SM2 5DA, UK.
1. Lee PN. "Marriage to a smoker" may not be a valid marker of
exposure in studies relating environmental tobacco smoke to risk of lung
cancer in Japanese non-smoking women. Int Arch Occup Environ Health
2. Yano E. Japanese spousal smoking study revisited: how a tobacco
industry funded paper reached erroneous conclusions. Tob Control
3. Lee PN. Japanese spousal study: a response to Professor Yano's
claims [Commentary]. Tob Control 2005;14:233-4.
4. Yano E. Response to P N Lee [Commentary]. Tob Control
5. Lee PN. Response to E Yano and S Chapman [Letter]. Tob Control
6. Yano E. Should a paper with erroneous interpretations based on
invalid measurements be published? [Letter]. Tob Control 2005;14:431-2.
7. Foulds J, Feyerabend C, Stapleton J, Jarvis MJ, Russell MAH.
Stability of nicotine and cotinine in unfrozen plasma. J Smoking-Related
8. Greeley DA, Valois RF, Bernstein DA. Stability of salivary
cotinine sent through the U.S. mail for verification of smoking status.
Addict Behav 1992;17:291-6.
9. Hagan RL, Ramos JM, Jr., Jacob PM, III. Increasing urinary
cotinine concentrations at elevated temperatures: the role of conjugated
metabolites. J Pharm Biomed Anal 1997;16:191-7.
10. Lee PN, Forey BA. Misclassification of smoking habits as a
source of bias in the study of environmental tobacco smoke and lung
cancer. Stat Med 1996;15:581-605.
Editor: This correspondence is now closed