Affiliations of authors: School of Population Health, University of Queensland, Brisbane, Queensland, Australia (CB); Department of Social Medicine, University of Bristol, Bristol, England (CB); Channing Laboratory, Department of Medicine, Brigham and Womens Hospital and Harvard Medical School, Boston, MA (DF, FES, BAR, GAC); American Cancer Society, Atlanta, GA (MT); Departments of Environmental Health (FES), Epidemiology (EH, GAC), and Biostatistics (BAR), and Harvard Center for Cancer Prevention (GAC), Harvard School of Public Health, Boston
Correspondence to: Diane Feskanich, ScD, Channing Laboratory, Department of Medicine, Brigham and Womens Hospital and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115 (e-mail: diane.feskanich{at}channing.harvard.edu)
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
In this analysis, our aim was to test the hypothesis that women have higher rates of lung cancer than men, given equal smoking exposure, by analyzing new prospective data and by providing a review of all previously published prospective analyses. Our original findings are drawn from a direct comparison of lung cancer incidence rates from equivalent female and male cohort experiences, with common age ranges and follow-up periods. These data come from the Nurses Health Study of women and the Health Professionals Follow-up Study of men, which share an overlapping set of investigators and have similar protocols for gathering exposure and outcome information.
![]() |
SUBJECTS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The Nurses Health Study was established in 1976 when 121 700 female registered nurses, aged 3055 years, returned a mailed questionnaire. Ten years later, the Health Professionals Follow-up Study was similarly created with 51 529 male health professionals (dentists, optometrists, osteopaths, podiatrists, pharmacists, and veterinarians) aged 4075 years. The Nurses Health Study was approved by the Internal Review Board of the Brigham and Womens Hospital in Boston, and the Health Professionals Follow-up Study received Internal Review Board approval from the Harvard School of Public Health in Boston. Both studies were designed to allow prospective examination of the influences of lifestyle on the occurrence of disease, especially heart disease and cancers. Using mailed questionnaires, participants in both cohorts provided baseline information about their disease history and personal characteristics and behaviors, and every 2 years they have updated and extended these data and reported newly diagnosed diseases on follow-up questionnaires. From study initiation through 2000, only 6% of the person-years in each cohort have been lost to follow-up. Deaths are commonly reported by families or the postal service and are confirmed through the National Death Index; very few deaths (<2%) are missed (10).
For this analysis, a common baseline year, 1986, was used for both cohorts, with follow-up through 2000. The study populations consisted of the Caucasian cohort participants (<4% were non-Caucasian in each cohort) who were former or current smokers, aged 4075 years at baseline, and with no prior history of cancer (other than nonmelanoma skin cancer). We excluded non-Caucasian participants from our analyses because research and national data suggest that lung cancer incidence may vary by race, and we did not want this to interfere with our analyses of sex differences. Never smokers, who were excluded at baseline, constituted 45% of the Nurses Health Study cohort and 46% of the Health Professionals Follow-up Study cohort. Data from 60 296 Nurses Health Study women and 25 397 Health Professionals Follow-up Study men were analyzed. All together, these individuals contributed approximately 738 000 and 297 000 person-years, respectively, to this analysis.
Lung Cancer Cases
When a cohort member reported a diagnosis of lung cancer on the biennial questionnaire, we attempted to obtain a medical record for confirmation and to establish a precise date of diagnosis. For lung cancers identified from death reports, we also sought medical records in addition to death certificates. Between 1986 and 2000, 994 lung cancer diagnoses were reported among the Nurses Health Study women, and 319 were reported among the Health Professionals Follow-up Study men. Reported lung cancers that were determined to be a metastatic site, or were not lung cancer according to medical records, or for which we were unable to obtain sufficient information were excluded from analyses (4% in the Nurses Health Study, 2.5% in the Health Professionals Follow-up Study). The remaining 955 reports from the women and 311 reports from the men were considered lung cancer cases in this analysis. Most of these subjects were confirmed as having primary lung cancer by medical records (82% in the Nurses Health Study, 92% in the Health Professionals Follow-up Study). Those for whom we were unable to obtain clinical confirmation were confirmed in a second request to the participant or by death certificate information. Among the cases with identified histology, cancer types were reasonably similar for women (48% adenocarcinoma, 17% epidermal, 20% small-cell, and 7% large-cell) and for men (44% adenocarcinoma, 22% epidermal, 17% small-cell, and 15% large-cell).
Smoking Characteristics
On the initial Nurses Health Study and Health Professionals Follow-up Study questionnaires in 1976 and 1986, respectively, participants reported whether they were a current smoker or had ever smoked in the past. If they indicated they were a current smoker, they were asked for the number of cigarettes typically smoked per day. Nurses Health Study participants reported the age at which they began to smoke and, for former smokers, the age at which they stopped smoking and the number of cigarettes smoked per day before quitting. Health Professionals Follow-up Study participants were asked to report the number of cigarettes they smoked per day at specified ages (<15, 1519, 2029, 3039, 4049, 5059, 6069 years); the median age in the earliest period in which a cigarette quantity was reported was considered to be the age at start of smoking. Men who indicated that they were former smokers on the initial questionnaire also reported the number of years since quitting (<1, 12, 35, 69, 10 years).
On each subsequent biennial questionnaire, both Nurses Health Study and Health Professionals Follow-up Study participants reported whether they currently smoked and the number of cigarettes smoked per day. In analyses, we reclassified participants in each 2-year follow-up cycle by smoking status (current or former), by number of cigarettes smoked per day and smoking duration among current smokers, and by time since quitting among former smokers. For former smokers, we retained the number of cigarettes smoked per day before quitting. Pack-years were calculated for each cycle as the product of years of smoking and packs of cigarettes smoked per day (20 cigarettes per pack). On the 1986 questionnaires, current smokers in both cohorts reported their usual brand of cigarettes, and tar content was assigned to most brands on the basis of data from the Federal Trade Commission (11).
Height, Body Mass Index, and Dietary Intake
Height was reported on the initial cohort questionnaires, and body mass index (BMI, kg/m2) was calculated with each biennial report of body weight. Dietary intake was assessed every 4 years with a food frequency questionnaire (FFQ). The FFQ addressed the consumption of 23 vegetables and 15 fruits; participants were asked to report their usual frequency of consumption over the past year in terms of the stated serving sizes (12). In a comparison with two 1-week diet records, the FFQ performed reasonably well in ranking individual fruit and vegetable intakes (13).
Statistical Analysis
Participants in both cohorts contributed person-years from the return date of their 1986 questionnaire (mailed in January for the Health Professionals Follow-up Study and in June for the Nurses Health Study) until a report of lung cancer, a report of any other cancer except nonmelanoma skin cancer, attainment of 80 years of age, death, or the end of follow-up (January 2000 for the Health Professionals Follow-up Study and June 2000 for the Nurses Health Study). This period of time included seven questionnaire follow-up cycles. Participants did not contribute person-years to any follow-up cycle in which they were missing a designation of smoking status. All subjects were censored at age 80 because only the Health Professionals Follow-up Study men had reached this age during the follow-up period; the Nurses Health Study women reached a maximum age of 79 years.
Determining the best way to use interrelated smoking measures to define "dose" has been recognized as challenging (14). It is difficult to interpret duration of smoking when modeled simultaneously with current age because of their high correlation among continuing smokers (r = .77 in the Nurses Health Study). There is a lower correlation between pack-years and age (r = .40 in the Nurses Health Study), although for this analysis, we believe it is more precise to separate measurements of smoking intensity and duration rather than combining them as pack-years. By including current age, age at start of smoking, and time since quitting in our analyses, we account for smoking duration and, to some extent, for variations in early-life susceptibility.
The primary purpose of this investigation was to directly compare male and female incidence rates of lung cancer in groups with comparable smoking histories. To this end, we computed sex- and age-specific incidence rates by smoking status and within categories of number of cigarettes smoked per day, age at start of smoking, and time since quitting. For number of cigarettes smoked per day and age at start of smoking, the cut points were the approximate median values in the cohorts; for time since quitting, the choice of cut point was limited by the categorical assessment in the Health Professionals Follow-up Study. We then calculated age-adjusted incidence rates and standardized incidence rates adjusted for age plus these smoking factors by using a spreadsheet developed by Rothman (15). These rates were directly standardized to the person-year distribution of the Nurses Health Study (using the combined person-years of both cohorts made no material difference in the rate comparisons). We also computed rate ratios (RRs) to compare the age-adjusted and standardized incidence rates in women with those in men. The rate ratios and 95% confidence intervals (CIs) were computed from the same spreadsheet using the MantelHaenszel procedure.
To further examine potential differences in susceptibility to lung cancer by sex, we calculated hazard ratios (HRs) for lung cancer in women compared with men by using Cox proportional hazards models conditioned on age (in months) and on follow-up cycle. Proportionality was checked by testing for interaction between sex and age and between sex and follow-up cycle. Hazard ratios from models adjusted for smoking dose and duration using number of cigarettes smoked per day, age at start of smoking, and time since quitting were compared with models adjusted for pack-years of smoking instead of number of cigarettes smoked per day and age at start. Additional adjustments for height, BMI, and fruit and vegetable intake were also assessed.
To display the multivariable-adjusted incidence rates graphically by age and sex, we generated age-incidence curves based on a unified model with former and current smokers of both sexes. The model included the following factors: age, sex, smoking status, number of cigarettes smoked per day (last quantity before quitting, for former smokers), age at start of smoking, and time since quitting, plus an interaction between age and sex. Follow-up cycle was not included as a factor in the model so that the curves would represent the entire 19862000 follow-up period. Age was modeled using restricted cubic splines (16) and the optimal spline variables were chosen from 21-knot splines using the likelihood ratio test. Confidence bands around the curves were generated for the whole model, not merely the age-related portion (17).
Literature Search
We searched PubMed using various combinations of the terms "lung cancer," "smoking or cigarettes," and "gender or sex," and we extended the search by scanning linked publications and reference lists and by seeking expert opinions from other researchers. Studies meeting our criteria (prospective studies with the following properties: measures of individual smoking exposure, largely complete follow-up for lung cancer incidence or mortality, and direct comparisons of lung cancer risks in men and women) were reviewed for relevant findings. To allow simple display of summary data, direct female-to-male comparisons (HRs or RRs derived from smoking-adjusted incidence rates of lung cancer, similar to our estimates) were extracted where available or calculated if possible. In some instances, where only sex-specific relative risks were reported, authors were approached for supplementary information on the underlying rates or the relevant case- and person-year distributions.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Smoking and other characteristics of the Nurses Health Study women and the Health Professionals Follow-up Study men at baseline in 1986 are presented in Table 1. The men were somewhat older than the women (mean ages of 56.0 years and 52.9 years, respectively) and, over the 14 years of follow-up, there was an excess of person-years among men in their seventies (15%) compared with women in their seventies (8%) (data not shown in Table 1). At baseline, current smoking was more prevalent in women (38%) than in men (19%). In both cohorts, over 60% of the former smokers in 1986 had quit more than 10 years earlier. Men started smoking at an earlier age and smoked more cigarettes per day than women; thus, they had somewhat higher mean duration and more pack-years of smoking. By the end of follow-up in 2000, only 11% of the Nurses Health Study women and 6% of the Health Professionals Follow-up Study men were actively smoking (data not shown in Table 1).
|
|
|
In Table 4, we summarize the hazard ratios for lung cancer for women versus men from Cox proportional hazards models, using either number of cigarettes smoked per day plus age at start of smoking or with pack-years as summary measures of smoking exposure (all models with former smokers also included time since quitting smoking). Model 2, which mirrored the stratified data, produced an identical female-to-male ratio of lung cancer incidence among current smokers (HR = 1.11, 95% CI = 0.87 to 1.42) and a slightly higher ratio among former smokers (HR = 1.18, 95% CI = 0.93 to 1.49). Combining the current and former smokers resulted in a hazard ratio of 1.11 (95% CI = 0.95 to 1.31) for women compared with men. Substituting pack-years for number of cigarettes smoked per day and age at start of smoking (model 3) produced a somewhat lower hazard ratio among current smokers and a higher hazard ratio among former smokers. Neither BMI nor fruit and vegetable consumption were confounders in these analyses, and they were therefore not included in the proportional hazards models. Height was unrelated to risk of lung cancer among both women and men.
|
Figure 1, A and B, shows age-specific incidence curves for lung cancer for hypothetical groups of current smokers (smoke 1524 cigarettes per day, started smoking between 15 and 19 years of age) and former smokers (quit more than 10 years ago, smoked 1524 cigarettes per day before quitting, started smoking between 15 and 19 years of age). These incidence rates were generated from a single model and apply to the entire follow-up period from 1986 to 2000. For both current and former smokers, lung cancer incidence before age 60 was identical for women and men; after this age, rates began to diverge and became somewhat higher for women compared with men, although the differences were not statistically significant.
|
To explore whether any differences in lung cancer incidence between women and men could be explained by type of cigarettes smoked, we considered tar content of the brands reported at baseline in 1986. Mean total daily tar exposure (tar per cigarette [mg] x number of cigarettes smoked per day) was somewhat higher among the men (237 mg; range = 21165 mg) than among the women (207 mg; range = 21065 mg) because of the use of higher tar cigarettes and the greater number of cigarettes smoked per day among men. Lack of data on tar content of cigarettes in later years precluded direct assessment of the influence of tar yields via modeling.
Literature Review
The literature search yielded six prospective studies that examined lung cancer incidence (5,18) or mortality (6,7,1921) in both women and men (Table 5). Cancer Prevention Study I (CPS-I) (6) was omitted from our review because we lacked the smoking-adjusted female-to-male rate ratio that was provided for CPS-II (6,7). The classic studies of male and female doctors by Doll et al. (22,23) were also omitted because there were few lung cancers among women, who also had limited smoking exposure. The two studies of lung cancer incidence that we included (5,18) reported a relative effect (HR or RR), and one mortality study (CPS-II) (6,7) calculated a summary relative effect for us (Thun MJ: personal communication). Among the remaining mortality studies, we calculated an age- and smoking-adjusted rate ratio from the published data of one study (19) and, for the remaining two studies (20,21), we used additional data kindly provided by the authors (Marang-van de Mheen PJ: personal communication; Carstensen J: personal communication) to compare rates directly. These summary measures of the "female effect" were adjusted for smoking characteristics to varying degrees. All confirm the lack of excess lung cancer risk in females.
|
The other three mortality studies (1921) reported rate ratios for lung cancer separately for women and men and provided additional details of patterns of risk. In the Scottish cohort (21), relative risks were higher for men smoking up to 24 cigarettes daily and were similar for both sexes at higher smoking levels. In the reference groups of never smokers, males experienced one-third higher mortality from lung cancer than did females (32 per 100 000 versus 24 per 100 000; Marang-van de Mheen PJ: personal communication), making the actual risk discrepancies among smokers even more favorable to women than suggested by the rate ratios. In fact, at every smoking level, for all smokers and for inhalers alone, the age-standardized rates provided were higher for men than for women. [The authors (21) note that the higher relative risks in men are at least partly explicable by the earlier ages at which the men began to smoke.] In the Swedish cohort (20), sex-specific rates were consistently higher for men than for women across levels of frequency (number of cigarettes smoked per day) and ages of starting smoking, and lung cancer rates among never smokers were very similar for men and women (Carstensen J: personal communication). In apparent contrast to the foregoing studies, in a U.S. cohort (19), age-adjusted relative risks for both number of cigarettes smoked per day and (separately) duration of smoking were approximately double for women compared with men. However, the age-standardized rates of lung cancer mortality among reference groups of never smokers were strikingly different, being three times as high for men (24 per 100 000) as for women (8 per 100 000). The data were sufficiently detailed to allow direct calculation of age- and smoking-standardized rates and an adjusted rate ratio for women versus men (Table 5); this rate ratio fits the pattern of the other studies, i.e., it showed no excess risk among women.
Three of the earlier cohorts (57,19) presented some age- and dose-specific data. Virtually every comparison (including former as well as current smokers) showed women to have lower risks than men at the older ages, whereas our model suggested that the opposite may be true for former smokers.
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Selection and measurement error seem unlikely to have influenced our findings in any material way. Follow-up was very successful in both Nurses Health Study and Health Professionals Follow-up Study cohorts over the same time span, and measurement of outcomes was identical in both cohorts, with high rates of histologic confirmation of primary lung cancer. In both cohorts, smoking exposures were updated biennially from study initiation, although for the women, smoking histories were documented earlier and somewhat more precisely. For time since quitting, continuous data were available for the women, while data for men were limited to a categorical assessment, with 10 or more years as the highest category. To the extent that the time since quitting was different for the sexes among those who had stopped smoking 10 or more years ago, residual confounding could account for some of the interaction we observed between sex and age among the older former smokers. In three of the earlier cohorts (57,19), the risk of lung cancer in current and former smokers was not found to be higher for women than for men at older ages.
Two smoking-related factors of possible relevance were not accounted for in this analysis: depth of inhalation and tar content. The role of these factors in modifying smoking-driven risk is complex, controversial, and interrelated (24). If men inhaled more deeply than women and deeper inhalation increased risk of lung cancer, our analysis will have underestimated differences in susceptibility between the sexes. Some reassurance in this regard comes from other prospective studies, in which differences in risk between males and females were little changed when comparisons were restricted to inhalers (5,20,21). Similarly, risk differences may have been underestimated if men smoked cigarettes with higher tar content than those smoked by women, as indicated in our 1986 baseline data. However, the National Cancer Institute has reported that compensatory changes in smoking patterns, including depth of inhalation and puff frequency, reduce any theoretical benefit of lower-tar cigarettes (25). Although these reports are largely reassuring, we cannot claim to have compared men with women who have precisely the same epithelial exposures to tobacco carcinogens.
Although casecontrol studies produced the crucial initial observations that identified smoking as the cause of the lung cancer epidemic (3), comparisons of the underlying forces of morbidity in men and women are best served by directly contrasting the rates that emerge from similar exposures. This was the rationale for pursuing our investigation and the focus of our literature search. Data from the other six prospective studies (57,1821), covering varying populations, time periods, smoking histories, follow-up procedures, and analytic approaches, offer no support for the hypothesis that women are generally more susceptible to lung cancer given the same smoking exposure as men. The previous prospective analysis that corresponded most closely with our own modeling approaches yielded a hazard ratio of 0.94 for lung cancer for female compared with male ever smokers in the CARET study (18), and the other follow-up of incident events (5) reported a relative risk for women of 0.8 with adjustment for age, inhalation, and pack-years of smoking. This result was essentially unchanged after adjusting for use of filter-tip cigarettes, and it was similar for all histologic types of lung cancer. Including our own result of an overall hazard ratio of 1.11 for lung cancer for women compared with men, the findings of the three incidence studies cluster tightly around the null, based on more than 3000 cases. Further, because lung cancer survival is so poor, mortality rates are nearly as good as incidence rates for capturing the underlying force of morbidity, so the estimates from the four mortality studies add substantial evidence against the existence of any heightened susceptibility for females. Indeed, taken at face value, the results of the four studies suggest a slight effect in the other direction.
The few results from previous prospective studies on comparative risks of lung cancer at older ages, including some among former smokers, show no hint of effect modification by sex, although it should be acknowledged that exposure data and numbers are limited. Similarly, for possible differential sex effects across histologies, neither the prospective data of Prescott et al. (5) nor the meta-analysis of Khuder (4) suggest any excess risk of adenocarcinoma among women. Nonetheless, further prospective monitoring of differences in smoking-related adenocarcinoma by sex seems sensible.
In summary, our direct research findings lend little support to the notion of modification of the tobacco effect by sex, but they are neither sufficiently precise nor complete enough to conclusively argue the case for equal risk of lung cancer for men and women who experience identical smoking exposure. However, in the context of what is now a substantial body of prospective evidence, it becomes very difficult indeed to argue the case for inequality of smoking-related lung cancer susceptibility. There does not seem to be either the need for or a point to pursuing biologic or other explanations for a hypothetical greater susceptibility to lung cancer among women. The continuing convergence of smoking patterns and lung cancer rates among men and women (26) points to the primary need to focus broadly on enhancing preventive interventions that will have similar relevance for all.
![]() |
NOTES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
We thank Dr. Perla Marang-van de Mheen and Prof. John Carstensen for help with deriving the female-to-male lung cancer rate ratios from their study data.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1 Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst1996;88:18392.
2 Perneger TV. Sex, smoking, and cancer: a reappraisal. J Natl Cancer Inst2001;93:16002.
3 Thun MJ, Henley SJ, Calle EE. Tobacco use and cancer: an epidemiologic perspective for geneticists. Oncogene2002;21:730725.[CrossRef][ISI][Medline]
4 Khuder SA. Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis. Lung Cancer2001;31:13948.[CrossRef][ISI][Medline]
5 Prescott E, Osler M, Hein HO, Borch-Johnsen K, Lange P, Schnor P, et al. Gender and smoking-related risk of lung cancer. Copenhagen Center for Prospective Population Studies. Epidemiology1998;9:7983.[ISI][Medline]
6 Thun MJ, Day-Lally CA, Calle EE, Flanders WD, Heath CW. Excess mortality among cigarette smokers: changes in a 20-year interval. Am J Public Health1995;85:122330.[Abstract]
7 Thun MJ, Myers DG, Day-Lally C, Namboodiri MM, Calle EE, Flanders WD, et al. Chapter 5. Age and the exposure-response relationships between cigarette smoking and premature death in Cancer Prevention Study II. In: Burns DM, Garfinkel L, Samet J, editors. Smoking and Tobacco Control Monograph No. 8: Changes in cigarette-related disease risks and their implication for prevention and control. Bethesda (MD): U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute; 1997. p. 383413. NIH Publ No. 97-4213.
8 Shriner SP, Bourdeau HA, Gubish CT, Tirpak DL, Davis AL, Luketich JD, et al. Sex-specific expression of gastrin-releasing peptide receptor: relationship to smoking history and risk of lung cancer. J Natl Cancer Inst2000;92:2433.
9 Fasco MJ, Hurteau GJ, Spivak SD. Gender-dependent expression of alpha and beta estrogen receptors in nontumour and tumour lung tissue. Mol Cell Endocrinol2002;188:12540.[CrossRef][ISI][Medline]
10 Rich-Edwards J, Corsano K, Stampfer M. Test of the National Death Index and Equifax Nationwide Death Search. Am J Epidemiol1994;140:10169.[Abstract]
11 Federal Trade Commission. Report of tar and nicotene content of smoke of 167 varieties of cigarettes. Washington (DC): Federal Trade Commission; 1978.
12 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 Inst2000;92:181223.
13 Feskanich D, Rimm EB, Giovannucci EL, Colditz GA, Stampfer MJ, Litin LB, et al. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J Am Diet Assoc1993;93:7906.[ISI][Medline]
14 Leffondre K, Abrahamowicz M, Siemiatycki J, Rachet B. Modeling smoking history: a comparison of different approaches. Am J Epidemiol2002;156:81323.
15 Rothman K. Episheet. Available at: http://members.aol.com/krothman/episheet.xls. [Last accessed: April 12, 2004.]
16 Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med1989;8:55161.[ISI][Medline]
17 Greenland S, Michels KB, Robins JM, Poole C, Willett WC. Presenting statistical uncertainty in trends and dose-response relations. Am J Epidemiol1999;149:107786.[Abstract]
18 Bach PB, Kattan MW, Thornquist MD, Kris MG, Tate RC, Barnett MJ, et al. Variations in lung cancer risk among smokers. J Natl Cancer Inst2003;95:4708.
19 Friedman GD, Tekawa I, Sadler M, Sidney S. Chapter 6. Smoking and mortality: the Kaiser-Permanente experience. In: Burns DM, Garfinkel L, Samet J, editors. Smoking and Tobacco Control Monograph No. 8: Changes in cigarette-related disease risks and their implication for prevention and control. Bethesda (MD): U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute; 1997. p. 47799. NIH Publ No. 97-4213.
20 Nilsson S, Carstensen JM, Pershagen G. Mortality among male and female smokers in Sweden: a 33 year follow up. J Epidemiol Community Health2001;55:82530
21 Marang-van de Mheen PJ, Davey Smith G, Hart CL, Hole DJ. Are women more sensitive to smoking than men? Findings from the Renfrew and Paisley study. Int J Epidemiol2001;30:78792.
22 Doll R, Peto R. Mortality in relation to smoking: 20 years observations on male British doctors. Br Med J1976;2:152536.[ISI][Medline]
23 Doll R, Gray R, Haffner B, Peto R. Mortality in relation to smoking: 22 years observations on female British doctors. Br Med J1980;280:96771.[ISI][Medline]
24 Thun MJ, Burns DM. Health impact of "reduced yield" cigarettes: a critical assessment of the epidemiological evidence [published erratum appears in Tob Control 2002;11:85]. Tob Control2001;10 (Suppl 1):i411.
25 Benowitz NL. Compensatory smoking of low-yield cigarettes. In: Shopland DR, Burns DM, Benowitz NL, Amacher RH, editors. Smoking and Tobacco Control Monograph No. 13: Risks associated with smoking cigarettes with low machine-measured yields of tar and nicotine. Bethesda (MD): U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health; 2001. p. 3963. NIH Publ No. 02-5047.
26 Jemal A, Travis WD, Tarone RE, Travis L, Devesa SS. Lung cancer rates convergence in young men and women in the United States: analysis by birth cohort and histologic type. Int J Cancer2003;105:1017.[CrossRef][ISI][Medline]
Manuscript received November 10, 2003; revised April 1, 2004; accepted April 14, 2004.
This article has been cited by other articles in HighWire Press-hosted journals:
Correspondence about this Article
Editorial about this Article
![]() |
||||
|
Oxford University Press Privacy Policy and Legal Statement |