Physical Activity, Obesity, and Risk for Colon Cancer and Adenoma in Men

Westernization or industrialization leads to an increase in rates of colon cancer, which is the second leading cause of malignant death in the United States [1]. Although the precise causes of colon cancer remain unclear, a diet high in red meat or animal fat and low in fruits and vegetables appears to increase the risk for this malignancy [2, 3]. It is perhaps less well recognized that an inverse association between physical activity and risk for colon cancer has been seen in studies of occupational activity only [4-12] and of both job-related and recreational activity [13-23]. In addition, many studies have found an association between body mass and elevated risk for colon cancer in men; this association is weaker in women [24-33]. The fact that the association is stronger in men suggests that the abdominal distribution of adiposity typical in men may be an important component of enhanced risk. More limited evidence suggests that height, which may be a proxy for a person's net energy intake during childhood and adolescence, is related to a higher risk for colon cancer [33-35]. We examine the association between physical activity, obesity, and attained height in relation to risk for colon cancers and their precursory adenomas in a large cohort of male health professionals in the United States. Waist and hip circumferences were available for a subcohort of the study population. We address the hypotheses that physical inactivity, obesity, and height increase the risk for colon cancer and adenoma independently of each other and of diet, and that the abdominal pattern of obesity is an additional independent risk factor. Methods Study Population The Health Professionals Follow-up Study [36] was started in 1986; in that year, 51 529 male dentists, optometrists, osteopaths, podiatrists, pharmacists, and veterinarians in the United States between 40 and 75 years of age responded to a mailed questionnaire. They reported on their leisure-time physical activity (described below); current body weight; weight at age 21 years; height; history of cancer and other medical conditions; parental history of various diseases, including colorectal cancer; and use of aspirin and other nonsteroidal anti-inflammatory medications. They also reported dietary and alcohol intake using a validated [37, 38], semi-quantitative food-frequency questionnaire. We mailed an optional questionnaire in 1987 to assess waist and hip circumferences. In 1988, 1990, and 1992, we updated exposure information and ascertained newly diagnosed medical conditions and history of colonoscopy or sigmoidoscopy, including the indications for endoscopy: bleeding in stool, positive results from tests for occult fecal blood, abdominal pain, diarrhea or constipation, family history of colorectal cancer, routine screening without symptoms, or follow-up [39]. Most of the deaths in the cohort were reported by family members or by the postal system in response to the follow-up questionnaires. We also used the National Death Index to identify deaths among nonrespondents [40]. Assessment of Physical Activity The 1986 questionnaire included a section about mainly recreational or leisure-time physical activity. The reliability and validity of questionnaires designed to assess physical activity have been investigated [41-43]. A questionnaire such as the one used in our cohort was evaluated in a cohort of U.S. nurses and was found to provide useful information [44], and similar results were found during a similar validation study done within the Health Professionals cohort (Chasan-Taber S. Personal communication). Participants reported the average time per week spent doing each of eight moderate and vigorous activities, choosing from among 10 possible responses that ranged from 0 minutes to 11 or more hours per week. The specific activities listed were walking or hiking outdoors (including walking during golf); jogging (slower than 10 minutes/mile); running (10 minutes/mile or faster); bicycling (including that done on a stationary machine); lap swimming; tennis, squash, or racquetball; and calisthenics or rowing. In addition, each respondent reported the number of flights of stairs he climbed daily and his usual walking pace. The reported time spent at each activity per week was multiplied by its typical energy expenditure requirements expressed in metabolic equivalents (METs) [45] to yield a MET-hour score. One MET, which is the energy expended by sitting quietly, is equivalent to 3.5 mL of oxygen uptake per kilogram of body weight per minute for a 70-kg adult. For example, 1 hour per week of running contributed 10.2 MET-hours, 1 hour of tennis contributed 6 MET-hours, and 1 hour of walking at a moderate pace contributed 3.2 MET-hours. Body weight was excluded from the derivation of energy expenditure from physical activity to avoid confounding the expenditure variable by body weight. If more than one published intensity level was available for a given activity, the moderate or general MET value was chosen. An average MET value was assigned to the categories that listed more than one activity, such as rowing or calisthenics, and squash or racquetball. Assessment of Anthropometric Variables Each man reported his current weight and height and his weight at age 21 years on the 1986 questionnaire. In 1987, we mailed an optional questionnaire once to obtain additional exposure information, including body circumference measurements. We instructed each participant to measure (to the nearest quarter inch) his waist at the umbilicus and his hips at the largest circumference between the waist and thighs while standing and without measuring over bulky clothing [46]. We provided a tape measure and an illustration to help standardize the measurements. Sixty-five percent of the cohort responded. We used the Quetelet index (kilograms/height in meters2) as a measure of total adiposity, waist-to-hip ratio to measure relative distribution of fat, and waist circumference to estimate total abdominal fat. Although the waist-to-hip ratio has been used more widely, waist circumference provides an estimate of absolute abdominal adiposity, the component most closely related to important metabolic abnormalities, including hyperinsulinemia, hypertension, and high triglyceride levels. To remove extraneous variation in the waist circumference because of height (taller men tend to have larger waist circumferences due to their larger body size rather than to obesity), we adjusted waist for height using residual analysis [47]. We first regressed waist on height using multiple linear regression and then added the residual to the average waist size (37.4 inches) for a man of average height (70 inches) to convert this measure back to the initial scale. This conversion created for each man a standardized waist circumference unconfounded by height. We evaluated the precision of self-reported anthropometric measures among 123 cohort members who were part of a dietary validation study [46]. Trained technicians paid the substudy participants two visits, approximately 6 months apart, to measure current weight and waist and hip circumferences. The Pearson correlation between self-report and the average of the technicians' two measurements was 0.97 for weight, 0.95 for waist circumference, 0.88 for hip circumference, and 0.69 for waist-to-hip ratio. The men's self-measurements of their waist circumferences were 0.36 inches greater, their self-measurements of hip circumferences were 0.78 inches smaller, and their self-measurements of weight were 2.3 pounds less than the technician's measurements. Identification of Patients with Colorectal Cancers In 1988, 1990, and 1992, we asked each participant whether cancer had been diagnosed during the previous 2 years. The response rate to the follow-up questionnaires was 94% through 31 January 1992. When a participant (or a decedent's next-of-kin) reported a diagnosis of cancer of the colon or rectum, we sought permission to obtain hospital records and pathology reports. A study physician, blinded to exposure information, reviewed all medical records received and extracted data about histologic type, anatomic location, and stage of the cancer. Proximal colon cancers were defined as those from the cecum to and including the splenic flexure, and distal colon cancers were defined as those in the descending and sigmoid colon. We confirmed 249 new cases of colorectal adenocarcinoma (excluding carcinoma in situ), 90% by medical records and the remainder with corroborating information about diagnosis and treatment from the cohort member. Two hundred three cancers were in the colon and 46 were in the rectum. Identification of Patients with Colorectal Adenomas and Controls Because more than 90% of the adenomas were diagnosed during endoscopic procedures for screening or for unrelated gastrointestinal conditions, we restricted the adenoma analysis to men who had had a colonoscopy or sigmoidoscopy. This was done to reduce the potential for detection bias. Most procedures were sigmoidoscopies; thus, we analyzed only adenomas of the distal colorectum. Although we did not examine proximal colon adenomas, this should not have biased inferences for the distal colorectum. However, different causes for proximal adenomas may exist. A total of 12 879 men who did not meet any of the exclusion criteria (see Data Analysis) reported having had an endoscopy between 1986 and 1992. In 1993, we sent a mailing to a random sample of 200 controls (men who reported negative results from an endoscopy) to confirm that they did not have adenomas. After one mailing, 140 (70%) controls granted us permission to review the medical records of their endoscopic procedure; none had an unreported, histologically confirmed adenoma. We were able to recontact 96% of the men who reported a diagnosis of polyp, and we received medical records in response to more than 96% of the requests sent to medical record departments, phys