An International Search for Causative Factors of Colorectal Cancer

Abstract

Colorectal cancer is the second leading cause of death from cancer in the United States today. The American Cancer Society expects 155,000 new cases of colorectal cancer and over 60,000 deaths from this cancer in 1990 (7). Because colorectal cancer is a high-impact disease and because therapy has resulted in limited success, more attention needs to be directed toward identifying its etiologic factors. The article by Whittemore et al. (2) in this issue of the Journal is a timely and significant contribution toward this goal. Although dietary studies are difficult to do because of the wide varieties of foods consumed, dietary study methods have improved significantly over recent years (3). It has been shown that well-designed dietary questionnaires can generate biologically meaningful data in an epidemiologic setting (4). Migrant population studies among the Japanese in Hawaii and others indicate that changes in environmental exposures affect colorectal cancer rates more rapidly than they affect the rates for breast or stomach cancer (5). Correspondingly, diet is one of the factors that has changed appreciably in migrant populations. These observations indicate that a current study of diet and large bowel cancer in migrants may be informative, especially compared with studies done in earlier years with more limited dietary methods. Even though some of the epidemiologic features of colon cancer and rectal cancer are distinct, it is still common practice to study both cancers simultaneously. Past case-control studies and prospective studies of diet and colorectal cancer have found that this cancer is positively associated with a high fat intake, especially from saturated fat (6). However, a number of other studies have not agreed with this finding (6). If the ingestion of dietary fat increases large bowel cancer risk, this finding has to be reconciled with other observations. For example, Mormons and Polynesians have levels of fat consumption similar to those of neighboring Caucasian populations, but their colorectal cancer risk is noticeably lower (7). Because high-fat diet fosters obesity (8), a positive association between obesity and colorectal cancer risk would provide supportive evidence of the high fat-colorectal cancer link, especially since body weight and Quetelet's index (weight in kilograms divided by the square of height in meters), as indicators of obesity, are more reproducible measurements than dietary histories. Some (9,70) but not all (77) prospective studies suggest that obesity is related to an increase in colorectal cancer risk. When present, the association appeared to be stronger in men than in women. The cohort study of Seventh-Day Adventists is especially revealing (72). Adventists consumed less fat and were less obese than non-Adventists. Their colorectal cancer rates were also low, but those who were obese had a 1.6-fold increase in colorectal cancer risk. A number of parameters have been used in epidemiologic studies to measure obesity, such as relative weight, body weight, and Quetelet's index, to name a few. Part of the inconsistency in results from past investigations of obesity could be due to the use of different measures of obesity. Furthermore, it has been pointed out that Quetelet's index reflects both the weight of lean tissue and the weight of fat tissue (75). There is growing interest in body fat distribution and in the use of advanced methods to measure more precisely the percentage of body fat, both subcutaneous and visceral (14). With the development of improved technology to measure body fat, epidemiologic researchers should be better able to relate obesity to colorectal cancer risk.