BRIEF COMMUNICATION

Lifetime Cigarette Smoking and Colorectal Cancer Incidence in the Physicians' Health Study I

Til Stürmer, Robert J. Glynn, I-Min Lee, William G. Christen, Charles H. Hennekens

Affiliations of authors: T. Stürmer, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Harvard School of Public Health, Boston, and Department of Epidemiology, University of Ulm, Germany; R. J. Glynn, I-M. Lee, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, and Harvard School of Public Health; W. G. Christen, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School; C. H. Hennekens, Departments of Medicine and Epidemiology and Public Health, University of Miami School of Public Health, Miami, FL.

Correspondence to: Robert J. Glynn, Sc.D., Ph.D., Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave. East, Boston, MA 02215–1204 (e-mail: rglynn{at}rics.bwh.harvard.edu).

Colorectal cancer ranks fourth in incidence and second in cause of death from cancer in the United States (1). Although virtually every study has reported a positive association between cigarette smoking and adenomatous polyps, the evidence regarding smoking and colorectal cancer is less clear, probably because of a long induction period (2). We, therefore, examined lifetime smoking history and incidence of colorectal cancer in a large cohort of men followed for more than 12 years.

In 1982, a total of 22 071 U.S. male physicians, 40–84 years of age, who did not have a history of myocardial infarction, stroke, cancer, liver or renal disease, gout, peptic ulcer, or contraindications to aspirin were randomly assigned in the Physicians' Health Study I, after written informed consent was obtained from them (3,4). The study was approved by the institutional review board of the Brigham and Women's Hospital, Boston, MA. Twice in the first year and once yearly thereafter, the participants completed a short questionnaire that asked about the occurrence of relevant health outcomes. The analysis is based on all self-reported and confirmed reports of colorectal cancer until December 31, 1995.

At baseline, 22 011 (99.7%) physicians reported whether they had ever smoked cigarettes regularly (never, past only, or current), and current smokers were asked how many cigarettes per day they smoked. In the 5-year questionnaire, former smokers were asked for the ages at which they started smoking (also current smokers) and stopped smoking and the number of packs of cigarettes smoked per day. Pack-years of smoking were defined as the number of years of smoking during different age and time periods multiplied by the average number of packs of cigarettes smoked daily.

Current and former cigarette smoking was reported by 2436 and 8666 physicians, respectively (Table 1Go). Former smokers were older than current and never smokers. Daily alcohol consumption was more prevalent in current smokers than in former or never smokers. Vigorous exercise was most common in never smokers and least common in current smokers. The mean numbers of servings of vegetables and fruits per day were very similar across all smoking categories. Current smokers had smoked a mean of 36.4 pack-years compared with 21.4 pack-years among former smokers. This difference was almost entirely because of smoking after age 30 years or within 20 years before baseline. The median age at starting smoking was equal in both groups. The median age at quitting smoking in former smokers was 37 years.


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Table 1. Baseline characteristics of the cohort of 22 011 physicians according to smoking status
 
Current smokers had almost double the risk for colorectal cancer compared with never smokers (adjusted relative risk [RR] for current smokers = 1.81; 95% confidence interval [CI] = 1.28–2.55; Table 2Go). When we took the number of cigarettes smoked into account, an adjusted RR of 2.14 (95% CI = 1.45–3.14) was observed among those who currently smoked 20 cigarettes or more per day. Smokers with the greatest number of pack-years (>40 pack-years) had the highest RR, but increased risk was also observed among smokers of fewer than 10 pack-years. When we looked at smoking before age 30 years, the increase in risk was most pronounced for less than or equal to 5 pack-years (RR = 1.52; 95% CI = 1.07–2.16) and 10–15 pack-years (RR = 1.72; 95% CI = 1.25–2.38). The number of pack-years of cigarette smoking after the age of 30 years was also associated with the risk of colorectal cancer. Consideration of pack-years smoked up to 20 years before baseline found RRs of about 1.5 for smokers with more than 10 pack-years. Nevertheless, there was also an association between pack-years smoked within 20 years before baseline, especially for smoking more than 15 pack-years during that period (RR = 1.56; 95% CI = 1.13–2.16).


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Table 2. Relative risk (RR) for colorectal cancer according to smoking status, dose, and amount smoked during different age and time periods
 
In this large cohort study of more than 22 000 healthy men aged 40–84 years who were followed for more than 12 years, cigarette smoking was an independent risk factor for colorectal cancer incidence. The strongest risk was observed in current smokers of 20 cigarettes or more per day, but cumulative lifetime exposure and exposure during various periods of life also increased the risk of colorectal cancer.

Our results are in accordance with findings from other published large cohort studies of colorectal cancer incidence in men (5,6), in women (7), and in both sexes (8,9). They are also in accordance with results from the largest cohort study to date examining smoking and colorectal cancer mortality in U.S. veterans (10) and from several recent case–control studies (1115). Our finding that smoking at all ages was associated with an increased risk of colorectal cancer appears to differ from the findings of Giovannucci et al. (5,7). This apparent discrepancy might be partly because of the observed strong correlations between total pack-years smoked and amount smoked in the recent past and in the distant past (data not shown). Our results are in agreement with the hypothesis that the amount smoked in the distant past is the main risk factor for colorectal cancer but also suggest that the amount smoked in the recent past might not be completely irrelevant.

Because the study was not specifically designed to test the hypothesis, information on the number of cigarettes smoked in different time periods was not collected. Although this is likely to obscure any changes in smoking habits, the number of cigarettes smoked per day has been shown to be quite constant over time (16), and any misclassification would tend to bias results toward the null. In contrast to studies with extensive dietary assessments, we could only control for intake of vegetables and fruits, which are most likely to be protective with regard to colorectal cancer (2,17), but, like others (5,7), we found little confounding by diet of the association between smoking and colorectal cancer risk. We could not control for colorectal cancer screening, but any differences in screening behavior between smokers and nonsmokers are likely to be less pronounced in physicians participating in a trial of primary prevention (aspirin and ß-carotene) than in other cohorts. Finally, our results pertain to men; however, with the exception of hormone replacement therapy (18), there is little evidence for differences in risk factors for colorectal cancer between men and women.

The totality of evidence supports the position that smoking is a risk factor for colorectal cancer. The finding that past and current smoking is associated with an increase in risk may imply that smoking reduction at any age would reduce the risk of developing colorectal cancer, the second leading cause of cancer death in many countries, including the United States.

NOTES

Supported by Publc Health Service grants R01CA34944 and R01CA40360 (National Cancer Institute) and R01HL26490 and R01HL34595 (National Heart, Lung, and Blood Institute), National Institutes of Health, Department of Health and Human Services.

Present address: T. Stürmer, Department of Epidemiology, German Centre for Research on Ageing, Heidelberg.

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Manuscript received December 6, 1999; revised April 20, 2000; accepted May 3, 2000.


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