© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 4, 308-309,
February 20, 2002
© 2002 Oxford University Press
CORRESPONDENCE |
Re: Sex, Smoking, and Cancer: a Reappraisal
Correspondence to: Edith A Zang, Ph.D., American Health Foundation, 300 East 42nd St., 5th Floor, New York, NY 10017 (e-mail: ezang{at}ahf.org).
In his commentary (1), Perneger claims that our reports (2,3) and those of other investigators (4,5) of a sex difference in smoking-related lung cancer risk are incorrect, because they were based on "misunderstandings about the meanings of relative risk versus absolute risk and the meanings of statistical interaction versus biologic interaction." In response to this statement, it is important to point out that, unlike other risk factors, cigarette smoking is the major cause of lung cancer and only a relatively small percentage of never smokers develop this disease. Therefore, the greater susceptibility to tobacco carcinogens for women implied by our relative risk estimates, coupled with their recent increase in smoking rates compared with those of men, indicate that the incidence of lung cancer in women may equal, or even surpass, that in men in future decades. To dismiss, on minor semantic grounds, findings that were confirmed by several recent studies, is to ignore a potential public health issue that merits further investigation.
More specifically, Perneger's critique seems to reflect a misinterpretation of our methods. Because all odds ratios were separately calculated for males and females in both of our studies (2,3), "relative risks of cancer for women versus men" were never directly estimated. In addition, as males and females were never combined in the same analysis, we could not have estimated the "statistically significant interaction" between smoking and sex that Perneger cites as one of the major reasons behind the "misinterpretation" of our results. In fact, we computed only sex-specific odds ratios and showed that they were consistently higher in women than in men at every level of lifelong exposure to cigarette smoking. In general, Perneger's assertion that our conclusions are incorrect because the data came from a sex-matched case–control study has no methodological basis. In our study, the relative risk of males versus females was never directly estimated, and the risk factor in the odds ratios was exposure to tobacco smoke rather than sex.
As a final point, Perneger disputes the conclusion by Castelao et al. (5) that women are at greater risk of bladder cancer than are men, by citing "contradictory" estimates of an equal or higher incidence in male versus female "ever smokers" and "never smokers." Rather than contradicting Castelao's findings, these incidence rates represent a classic example of why sex differences in susceptibility to tobacco carcinogens have so long been overlooked and misinterpreted; namely, whenever exposure to cigarette smoking is merely recorded as "ever smokers" versus "never smokers" without considering dose, the exposure of men will consistently be underestimated compared with that of women, and the risk of men will be consistently overestimated compared with that of women.
The reason for this result is that, in past decades, men on average have smoked more cigarettes and have chosen brands with higher yields of tar than have women. Thus, Perneger's reasoning overlooks the fact that the equal or higher incidence of bladder cancer in male ever smokers is probably a result of their greater exposure to cigarette smoking and, possibly, to other bladder cancer risk factors, such as alcohol use. On the other hand, women's higher susceptibility to tobacco carcinogens than that of men is bound to be camouflaged when the exposure measure fails to incorporate dose.
REFERENCES
1
Perneger TV. Sex, smoking, and cancer: a reappraisal. J Natl Cancer Inst 2001; 93;1600–2.
2 Zang EA, Wynder EL. Cumulative tar exposure. A new index for estimating lung cancer risk among cigarette smokers. Cancer 1992;70:69–76.[CrossRef][Web of Science][Medline]
3
Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst 1996;88:183–92.
4
Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB. Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type. Am J Epidemiol 1993;138:281–93.
5
Castelao JE, Yuan JM, Skipper PL, Tannenbaum SR, Gago-Dominguez M, Crowder JS, et al. Gender- and smoking-related bladder cancer risk. J Natl Cancer Inst 2001;93:538–45.
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