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© 2004 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Are Women More Susceptible to Lung Cancer?
Affiliations of authors: International Epidemiology Institute, Rockville, MD, and Department of Medicine, Vanderbilt University and Vanderbilt-Ingram Cancer Center, Nashville, TN (WJB, JKM)
Correspondence to: William J. Blot, PhD, International Epidemiology Institute, 1455 Research Blvd., Ste. 550, Rockville, MD 20850, and Department of Medicine, Vanderbilt University and Vanderbilt-Ingram Cancer Center, 691 Preston Research Bldg., Nashville, TN 37232 (e-mail: blotw{at}cs.com)
Drs. Risch and Miller state that we (1) and Bain et al. (2) criticize their earlier case–control study of lung cancer, and they purport to offer an alternative explanation for the discrepancy between the findings of case–control and cohort studies examining differences in lung cancer risk between men and women. They state (we believe incorrectly) that whereas the case–control studies have addressed the statistical interaction between smoking and sex on the risk of lung cancer, the cohort studies have examined only the main effects of sex. They conclude that current evidence indicates that female smokers are more susceptible to smoking-induced lung cancer than male smokers.
We would not characterize our comments on the Risch et al. (3) case–control study as criticism; indeed, we simply described the study's findings of higher odds ratios among women than men across smoking categories. We did note that the focus of case–control studies is the estimation of relative risks of lung cancer among smokers compared with never smokers, whereas the cohort studies, including that of Bain et al. (2), compare actual incidence or mortality rates of lung cancer among men and women at similar levels of smoking. When the cohort studies examine rates of lung cancer among men and women with equivalent amounts smoked, they show consistently that the rates are about the same or even somewhat less for women. Thus, the studies clearly indicate that the probability of developing lung cancer is about the same in men and women when approximately equal smoking histories are considered.
Estimates of relative risk from case–control studies such as that of Risch et al. (3) are sensitive to variation in lung cancer risk among never smokers and, thus, the demonstration of effect modification by sex cannot automatically be interpreted as providing evidence for a difference in susceptibility by sex. The estimates of male–female differences in lung cancer incidence from cohort studies such as Bain et al. (2) are based only on smokers themselves and, to the extent that men and women have comparable exposure to tobacco carcinogens in the strata defined by smoking histories, these estimates provide a direct evaluation of gender differences in susceptibility. Risch and Miller argue that among never smokers, women tend to have lower rates of lung cancer than men. However, male and female nonsmokers may differ in numerous other ways that may influence their risk of lung cancer. Accounting for such occupational, environmental, lifestyle, medical, or other risk factors among nonsmokers is difficult, because smoking is such a dominant cause of lung cancer that there typically are only small numbers of case patients who have never smoked (4). Furthermore, in the cohort studies, if relative risks of lung cancer among smokers versus never smokers were to be calculated, they would not always be higher among females than males. Indeed, in the large CPS-II study cited in the tables presented by Bain et al. (2) and Risch and Miller, the male-to-female ratio in lung cancer rates was greater among smokers (adjusted for amounts smoked) than among nonsmokers.
Although it is not implausible that men and women may respond to tobacco carcinogens differently, the existing cohort studies, including that from Bain et al. (2), suggest that such differences have not had a marked effect on lung cancer rates. Thus, the conclusion of Risch and Miller that the "evidence to date indicates that female smokers are more sensitive than male smokers to the effects of smoking in inducing lung cancer" seems premature and not supported by the available cumulative epidemiologic data.
REFERENCES
1 Blot WJ, McLaughlin JK. Are women more susceptible to lung cancer? J Natl Cancer Inst 2004;96:812–3.
2 Bain C, Feskanich D, Speizer FE, Thun M, Hertzmark E, Rosner BA, et al. Lung cancer rates in men and women with comparable histories of smoking. J Natl Cancer Inst 2004;96:826–34.
3 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.
4 Blot WJ, Fraumeni JF Jr. Cancers of the lung and pleura. In: Schottenfeld D, Fraumeni JF Jr, editors. Cancer epidemiology and prevention. 2nd ed. New York (NY): Oxford University Press; 1996. p. 637–65.
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Del.icio.us What's this?
J Natl Cancer Inst 2004 96: 1560.
J Natl Cancer Inst 2004 96: 1561.
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