Affiliation of authors: C. Paris (Occupational Disease Department), J. Benichou (Department of Biostatistics), L. Thiberville (Pneumology Department), Rouen University Hospital, Rouen, France.
Correspondence to: Christophe Paris, M.D., Ph.D., Rouen University Hospital Charles Nicolle, 1 rue de Germont, 76031 Rouen Cedex, France (e-mail: christophe.paris{at}chu-rouen.fr).
Using autofluorescence endoscopy, Lam et al. (1) observed a lower prevalence of high-grade preinvasive bronchial lesions (i.e., moderate or severe dysplasia or carcinoma in situ) in women than in men (14% versus 31%), even after controlling for age, smoking, and overall lung function (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.04 to 0.88). Moreover, these authors found no difference in the prevalence of high-grade lesions between current and ex-smokers, even more than 10 years after smoking cessation. These findings contradict reports (2) of a higher risk of lung cancer occurrence in women than in men with similar smoking habits. They are also at odds with numerous reports [e.g., see (3)] of decreased lung cancer occurrence in former relative to current smokers.
These discrepancies may be explained by the inclusive definition of high-grade lesions used by Lam et al. and their lack of accounting for other factors associated with the existence and/or progression of high-grade lesions. Indeed, after using a more restrictive definition of high-grade lesions (i.e., severe dysplasia or carcinoma in situ only) and additionally adjusting for occupational exposure and personal lung cancer history, we obtained findings that were markedly different from those of Lam et al. by use of multivariable analysis of 228 subjects in our Early Detection Study (4,5) (Table 1). Relative to current smokers, adjusted ORs for the presence of high-grade lesions (n = 21) were 0.27 (95% CI = 0.05 to 1.4) and 0.07 (95% CI = 0.01 to 0.71) for short-term and long-term ex-smokers, respectively (P = .012, trend test). Although high-grade lesions were observed to be as prevalent in men as in women (9%), multivariable analysis revealed a trend for a higher prevalence in women (adjusted OR = 3.3, 95% CI = 0.39 to 27.7).
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These results suggest that including moderate dysplasia in high-grade lesions may weaken associations (e.g., with smoking cessation) or even reverse them (e.g., with sex). Experimental autograft animal studies have suggested a lower progression rate and a higher regression rate of moderate dysplasia when exposure to some tobacco carcinogens ceased (6), but it is unclear whether smoking cessation has any influence on the occurrence of moderate dysplasia or lower grade lesions. Additional findings from our data showing a lower rate of progression and a higher rate of regression for moderate dysplasia relative to severe dysplasia and carcinoma in situ argue in favor of using the more restrictive definition of high-grade lesions (5,7). Besides, the differential distribution of occupational exposure or personal lung cancer history, which we additionally included in multivariable analysis, may have contributed further to differences between our results and those of Lam et al.
Further studies are needed to better characterize factors associated with the presence of high-grade lesions of the bronchial epithelium to assist investigators in more reliably identifying high-risk subjects for inclusion in lung cancer early detection or chemoprevention programs.
We thank Philip Rousseau-Cunningham for his valuable advice in editing this manuscript. This research was supported by a Programme Hospitalier de Recherche Clinique grant from the French Department of Health (1996).
REFERENCES
1 Lam S, leRiche JC, Zheng Y, Coldman A, MacAulay C, Hawk E, et al. Sex-related differences in bronchial epithelial changes associated with tobacco smoking. J Natl Cancer Inst 1999;91:6916.
2 Wynder EL, Hoffmann D. Smoking and lung cancer: scientific challenges and opportunities. Cancer Res 1994;54:528495.[Medline]
3 Simonato L, Agudo A, Ahrens W, Benhamou E, Benhamou S, Boffetta P, et al. Lung cancer and cigarette smoking in Europe: an update of risk estimates and an assessment of inter-country heterogeneity. Int J Cancer 2001;91:87687.[CrossRef][Medline]
4 Paris C, Benichou J, Bota S, Sagnier S, Metayer J, Eloy S, et al. Occupational and non occupational risk factors of high grade bronchial preinvasive lesions. Eur Respir J 2003; 21:33241.
5 Bota S, Auliac JB, Paris C, Metayer J, Sesboüe R, Nouvet G, et al. Follow-up of bronchial precancerous lesions and carcinoma in situ using fluorescence endoscopy. Am J Respir Crit Care Med 2001;164:168893.
6 Hammond WG, Teplitz RL, Benfield JR. Variable regression of experimental bronchial preneoplasia during carcinogenesis. J Thorac Cardiovasc Surg 1991;101:8006.[Abstract]
7 Banerjee AK, Rabbitts PH, George PJ. Are all high-grade preinvasive lesions premalignant, and should they all be treated? Am J Respir Crit Care Med 2002;165:14523.
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