Smoking and Risk of Total and Fatal Prostate Cancer in United States Health Professionals 1 Edward Giovannucci, 2 Eric B. Rimm, Alberto Ascherio, Graham A. Colditz, Donna Spiegelman, Meir J. Stampfer, and Walter C. Willett Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 [E. G., E. B. R., G. A. C., M. J. S., W. C. W.], and Departments of Nutrition [E. G., E. B. R., A. A., M. J. S., W. C. W.], Epidemiology [E. G., E. B. R., A. A., G. A. C., D. S., M. J. S., W. C. W.], and Biostatistics [D. S.], Harvard School of Public Health, Boston, Massachusetts 02115 Abstract Studies that have examined the relationship between cigarette use and prostate cancer incidence have yielded inconsistent results, although most studies have suggested that smoking is related to the occurrence of fatal prostate cancer. We evaluated prospectively the relationship between cigarette smoking and total, distant metastatic, and fatal prostate cancer in 47,781 male health professionals throughout the United States followed with questionnaires. From 1986 to 1994, we documented 1369 men with prostate cancer (excluding stage A1). One hundred fifty-two of the men had distant metastatic disease at diagnosis, and 103 fatal cases occurred from 1986 to 1994. Early (before age 30), late (within recent 10 years), and lifetime cumulative smoking history were unrelated to risk of total prostate cancer. However, men who had smoked 15 or more pack-years of cigarettes within the preceding 10 years were at higher risk of distant metastatic prostate cancer [multivariate relative risk (RR), 1.81; 95% confidence interval (CI), 1.05–3.11; P (trend), 0.03] and fatal prostate cancer [RR, 2.06; CI, 1.08 –3.90; P (trend), 0.02] relative to nonsmokers. Within 10 years after quitting, the excess risk among smokers is eliminated. The higher rate of fatal prostate cancer among smokers did not appear to result from confounding by diet or other lifestyle factors, different screening behavior between smokers and nonsmokers, or from other smoking-related comorbidities. Our results indicate that although smoking was unrelated to prostate cancer incidence, recent tobacco use had a substantial impact on the occurrence of fatal prostate cancer. Introduction Cigarette use is the leading cause of death from cancer, but the relationship between smoking and prostate cancer has been inconsistent; some studies indicate no connection (1–5), whereas others suggest an elevated risk among smokers (6 –10). In several studies, smokers had higher mortality rates from prostate cancer (11–14). A large investigation of United States veterans (12) found an elevated risk among current smokers at baseline during the initial 8.5 years of follow-up, but this risk was attenuated over the 26-year follow-up. This finding sug- gests that only relatively recent use of tobacco influenced risk of prostate cancer mortality because many smokers quit over time. A possible explanation for the more consistent results for mortality than incidence is that smokers may delay diagnosis and treatment, which could result in poorer survival. Alterna- tively, tobacco may theoretically induce prostate cancers to develop a more aggressive phenotype or may cause the devel- opment of a distinct subset of rapidly progressive cancers. For example, smoking-related carcinogens could possibly cause mutations in genes associated with tumor progression, or to- bacco use may alter host factors, such as levels of hormones, which foster tumor progression. Indeed, two studies (15, 16) have found smokers more likely to be diagnosed with advanced stage or high histological grade prostate cancers. The studies that found smokers to be at higher risk for prostate cancer mortality (11–14) could not distinguish whether this association was a result of delayed diagnosis and treatment among smokers, failure to control for confounding factors, or from direct effects from tobacco use. To better understand the nature of the relationship between smoking and prostate cancer, we examined smoking history and this malignancy in the Health Professionals Follow-Up Study. Subjects And Methods The Study Population and Follow-Up of the Cohort. The Health Professionals Follow-up Study is an ongoing prospec- tive cohort study of the causes of cancer and heart disease in men (17). The cohort consists of 51,529 United States male dentists, optometrists, osteopaths, podiatrists, pharmacists, and veterinarians who were 40 –75 years when they responded to a mailed questionnaire in 1986. These men provided information on age, current and past tobacco use, marital status, height and weight, ancestry, medications, disease history, physical activ- ity, and diet. For this analysis, we excluded men who reported cancer at baseline (other than nonmelanoma skin cancer). Be- cause of the importance of controlling for dietary factors (17– 19), we included only men who adequately completed a food frequency questionnaire (97% of the total). After these baseline exclusions, 47,781 participants formed the cohort for analysis beginning in 1986. Follow-up questionnaires were sent in 1988, 1990, 1992, and 1994 to ascertain new cases of prostate cancer and to update exposure information. Most of the deaths in the cohort Received 7/16/98; revised 2/2/99; accepted 2/12/99. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported by Research Grants CA 55075 and HL 35464 from the NIH. 2 To whom requests for reprints should be addressed, at Channing Laboratory, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115. Phone: (617) 432-4648; Fax: (617) 432-2435; E-mail: edward.giovannucci@channing.harvard.edu. 277 Vol. 8, 277–282, April 1999 Cancer Epidemiology, Biomarkers & Prevention Research. on November 26, 2016. © 1999 American Association for Cancer cebp.aacrjournals.org Downloaded from