Affiliations of authors: H. A. Risch, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT; A. B. Miller, Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Correspondence to: Harvey A. Risch, M.D., Ph.D., Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College St., P.O. Box 208034, New Haven, CT 06520-8034.
In a recent issue of the Journal (1), Perneger criticizes us (2), as well as a number of other authors, for stating that casecontrol study results dealing with relative risks of cancer also apply to absolute risks of cancer. The studies in question concerned malefemale differences in risks of lung and bladder cancer according to cigarette smoking history. Our results did indeed show that female smokers had a higher relative risk of lung cancer compared with male smokers, at the same level of smoking (2), and we further concluded that female smokers had greater absolute risk of lung cancer than male smokers. Zang and Wynder (3) concluded similarly. Perneger is theoretically correct that the latter conclusion concerning absolute risks does not follow from the former one on relative risks. However, his criticism is wrong because its validity depends upon the male and female absolute risks for never smokers, i.e., the baseline category for the relative risks. That is, a high enough baseline lung-cancer risk among male never smokers compared with female never smokers could, in theory, account for our findings of twofold to threefold higher smoking-related relative risks for females (2). As we pointed out 7 years ago (4,5), data on these baseline absolute risks had been available for some time. At that time, nine studies had demonstrated that the difference in baseline risk between male and female never smokers is small and, therefore, cannot explain the twofold to threefold higher relative risks seen for females. This result has been confirmed by the Nurses Health Study/Health Professionals' Follow-up Study, with incidence rates among male and female nonsmokers of 10.1 and 12.2 per 100 000 per year, respectively (ratio 1.21) (6). In total, these 10 studies identified 1022 cases of lung cancer among nonsmoking males and 1832 among nonsmoking females. A combined precision-weighted estimate of the common female/male ratio of absolute age-adjusted rates from these 10 studies is 0.80 (95% confidence interval = 0.73 to 0.87). Even if we use a conservative value for this ratio equal to the lower 95% limit, the highest relative risk solely attributable to differing baseline risks is 0.731 = 1.37. Thus, twofold to threefold higher relative risks for female smokers compared with male smokers require that female smokers be at higher absolute risk than male smokers at the levels of cigarette smoking where these twofold to threefold relative risks occur. These levels are not very great, beginning at less than 5 pack-years (2) or 5 kg of tar (7).
The above evidence strongly suggests that women who have been regular smokers since young adulthood are at greater absolute risk of lung cancer than are men with the same smoking history, and they certainly are at greater risk than men relative to the risk levels they could achieve by not smoking. Contrary to Perneger's discussion (1), this conclusion does not depend on whether multiplicative, additive, or other regression models are used for analysis.
REFERENCES
1
Perneger TV. Sex, smoking, and cancer: a reappraisal. J Natl Cancer Inst 2001;93:16002.
2 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;138:28193.[Abstract]
3
Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst 1996;88:18392.
4 Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB. Lung cancer risk for female smokers. Science 1994;263:12068.[Medline]
5 Risch HA, Howe GR, Jain M, Burch JD, Holowaty EJ, Miller AB. Re: Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type. Am J Epidemiol 1994;140:1878.
6
Feskanich D, Ziegler RG, Michaud DS, Giovannucci EL, Speizer FE, Willett WC, et al. Prospective study of fruit and vegetable consumption and risk of lung cancer among men and women. J Natl Cancer Inst 2000;92:181223.
7 Harris RE, Zang EA, Anderson JI, Wynder EL. Race and sex differences in lung cancer risk associated with cigarette smoking. Int J Epidemiol 1993;22:5929.[Abstract]
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