The Association of Physical Activity and Body Mass Index with the Risk of Large Bowel Polyps Kristin Wallace, 2 John A. Baron, 1,2 Margaret R. Karagas, 2 Bernard F. Cole, 2 Tim Byers, 4 Michael A. Beach, 3 Loretta H. Pearson, 2 Carol A. Burke, 5 William B. Silverman, 6 and Robert S. Sandler 7 Departments of 1 Medicine, 2 Community and Family Medicine, and 3 Anesthesia, Dartmouth Hitchcock Medical Center, Lebanon, New Hamsphire; 4 Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado; 5 Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio; 6 Department of Medicine, University of Iowa, Iowa City, Iowa; and 7 Department of Medicine, University of North Carolina, Chapel Hill, North Carolina Abstract Purpose and Method: Several studies have suggested that physical inactivity and obesity increase the risk for colorectal neoplasia. In this study, we investigated the association of physical activity and body mass index (BMI) with the risk of different types of large bowel polyps. We did an observa- tional analysis nested within a randomized double-blind placebo-controlled chemoprevention trial among patients with one or more recently resected histologically confirmed colorectal adenoma. Nine hundred thirty patients were randomized to calcium (1,200 mg/d, as carbonate) or placebo. Follow-up colonoscopies were conducted approximately 1 and 4 years after the qualifying examination. At study entry, we obtained each subject’s current body weight and height, which we used to calculate BMI. After the second study colonoscopy, we asked subjects questions about their leisure time physical activity. Seven hundred eighty-seven subjects completed at least part of the physical activity questionnaire. Results: We found no association between measures of physical activity or BMI and tubular adenomas or hyper- plastic polyps. However, among men, there were strong inverse associations observed between physical activity and advanced neoplastic polyps. Compared with men whose total daily energy expenditure was in the lowest tertile, those in the highest tertile had a risk ratio of 0.35 (95% confidence interval, 17-0.72); there was no similar reduction observed among women (risk ratio, 1.21; 95% confidence interval, 0.36- 4.03; P for interaction = 0.04). Data Interpretations: We found a significant inverse rela- tionship between several measures of physical activity and risk of advanced colorectal neoplasms, particularly among men. No associations were found between BMI and hyperplastic polyps, tubular adenomas, or advanced neo- plastic polyps. (Cancer Epidemiol Biomarkers Prev 2005; 14(9):2082 – 6) Introduction Physical activity is strongly associated with a reduction in the risk of large bowel cancer (1, 2), whereas obesity has been linked to an increase in risk (3-5). A recent comprehensive review estimated that high levels of physical activity reduced the risk of colon or colorectal cancer by 40% to 50% (1) independently of body size. Conversely, high body mass index (BMI) levels have been associated with as much as a 2-fold increase in risk of colorectal cancer and with stronger associations observed in men (4, 5). Numerous studies have also examined the association of physical activity with colorectal adenomas—precursors to most colorectal cancers (6, 7). Many of these have reported strong to moderate effects for at least some measures of activity (3, 8-16), although a few reported only weak associations or no relation at all (17-21). Results from a number of studies suggest that the inverse association between physical activity may be stronger for subgroups of adenomas such as those that are large or severely dysplastic (3, 13, 16, 20). Increasing BMI levels have been associated with a higher risk of adenoma in many (3, 13, 16, 18, 20, 22-28), but not all, investigations (10, 17, 29). Several have observed an increased risk of large (13, 18, 20, 22, 24, 26) or advanced adenomas (large size, presence of villous histology, or severe dysplasia) with higher BMI (16, 23). However, data from large prospective studies are sparse, and virtually all the data refer to prevalent adenomas found at screening exams. To further evaluate these associations, we did an observational analysis nested within a large multicen- ter, double-blind, placebo-controlled trial of the effect of calcium supplementation on the recurrence of large bowel adenomas. Materials and Methods Our analysis is based on data from the Calcium Polyp Prevention Study, a randomized double-blind placebo con- trolled trial testing the effect of calcium carbonate supple- mentation (1,200 mg/d) on the recurrence of colorectal adenomas (30). We reviewed data on 2,918 apparently eligible subjects. We were unable to contact 223; 1,066 declined to participate; 510 were found to be ineligible; and 1 did not enroll for unknown reasons. After written consent had been obtained, the remaining 1,118 subjects began a 3-month placebo run-in period to assess their adherence to the study regimen. At the end of the run-in period, 930 subjects had taken at least 80% of their prescribed tablets, wished to continue the study, and were considered appropriate for randomization. Study participants were recruited at six clinical centers in the United States; each had a history of at least one histologically confirmed colorectal adenoma excised within the 3 months before entry and was shown to have no remaining polyps in the entire large bowel after complete colonoscopic examination. 2082 Cancer Epidemiol Biomarkers Prev 2005;14(9). September 2005 Received 10/24/04; revised 5/19/05; accepted 6/28/05. Grant support: NIH grants CA37287, CA23108, and CA46927-11. 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. Requests for reprints: John A. Baron, Professor of Medicine, and of Community and Family Medicine, Suite 300, 46 Centerra Parkway, Lebanon, NH 03756. Phone: 603-650-3456; Fax: 603- 650-3473. E-mail: john.a.baron@dartmouth.edu Copyright D 2005 American Association for Cancer Research. doi:10.1158/1055-9965.EPI-04-0757 Research. on September 20, 2021. © 2005 American Association for Cancer cebp.aacrjournals.org Downloaded from