Colon and Rectum continued	A number of studies have found an association between red meat consumption and colorectal cancer. The prospective study of nurses, for example, found that women with the highest ratio of red meat to chicken and fish intake had two and one-half times the colon cancer risk of those with the lowest ratio (Willett et al., 1990). A prospective cohort study of nearly 50,000 U.S. male health professionals showed that men who ate beef, pork, or lamb as a main dish, compared to those consuming these foods less than once a month, had over three times the risk of colon cancer (Giovannucci et al., 1994). Cooked meats have been found to contain compounds, including a class of heterocyclic amines, which are mutagenic and carcinogenic in animal models. They are produced during high-temperature cooking such as broiling or frying (Sugimura, 1986). Countries and regions with the highest per capita dietary fiber consumption tend to have the lowest colorectal cancer rates. A recent meta-analysis of 16 case-control studies found nearly a 35 percent reduction in the relative risk of colorectal cancer for those in the highest, compared to the lowest, category of dietary fiber intake (Trock, 1990). In the cohort study of polyps in male health professionals, men in the highest, relative to those in the lowest, category of dietary fiber intake had half the risk of developing an adenomatous polyp of the large bowel (Giovannucci et al., 1990). The large majority of case-control studies of colorectal cancer that assessed vegetable intake found it to be protective (Potter, 1993). Several case-control studies of large bowel cancer have shown an inverse association for fruit intake, but in general the analytic epidemiologic findings are not as consistent for fruits as for vegetables (Slattery et al., 1988). Because vegetables are a major source of dietary fiber in industrialized countries, the observed protective association for vegetables might be due to fiber or the joint effect of fiber and specific anticarcinogens found in vegetables. Recent investigations have suggested that intake of folic acid, found in many vegetables, may reduce the risk of colorectal cancer (Glynn and Albanes, 1994). One international correlation study has shown generally higher calcium consumption in countries with lower colorectal cancer rates, but the number of data points was rather small (Sorenson et al., 1988a). Garland and his colleagues spurred epidemiologic interest in this question with their report from the prospective Western Electric Study of an inverse calcium-large bowel cancer association (Garland et al., 1985), a finding confirmed in some but not all subsequent studies (Sorenson et al., 1988b). Some recent studies have observed that intake of vitamin D reduces colorectal cancer risk (Bostick et al., 1993). Several epidemiologic investigations have shown a direct association between alcohol ingestion and colorectal cancer, particularly for beer and rectal cancer, whereas other studies have found minimal or no association. A recent meta-analysis of 27 studies concluded that the increased risk of colorectal cancer in relation to alcoholic beverage consumption was at best small and not clearly indicative of a causal role (Longnecker et al., 1990). Colorectal cancer mortality in the United States has tended to be concentrated in regions of past intense industrial activity (North Atlantic Coast, New Jersey, Massachusetts, New York, and the urban Great Lakes area) (Spiegelman and Wegman, 1985). In a number of occupational cohort studies, colon cancer rates have been moderately increased (Lashner and Epstein, 1990). Data on potential occupational colorectal carcinogens, however, tend to be sparse and at the present time there is insufficient evidence to conclude that a substantial proportion of colorectal cancer incidence in the United States results from workplace exposure. A number of epidemiologic studies have now found that regular use of aspirin is associated with a reduced risk of colorectal cancer, although the evidence on this link is not wholly consistent (Garewal, 1994). Some epidemiologic and clinical studies have suggested that other nonsteroidal anti-inflammatory drugs (NSAID) may protect against colonic neoplasia. NSAID affect prostaglandin synthesis in humans and have been shown to inhibit chemically induced colorectal tumor formation in animal models (Pollard and Luckert, 1980; Metzger et al., 1984). The possible protective effect of aspirin and other NSAID on colorectal carcinogenesis is an active area of research. Other epidemiologic studies have found a small direct association between obesity and risk of large bowel malignancy (Wu et al., 1987). Because cancer itself may cause weight loss, it is important to ascertain weight some years prior to diagnosis. Case-control studies have found little association between height and large bowel cancer, but a direct association was observed in two cohort studies (Chute et al., 1991; Albanes et al., 1988). These cohorts, however, could not be said to reflect much range of nutritional deprivation, and therefore a nutritional explanation for these height-colorectal cancer findings is tenuous. An association between low physical activity and large bowel malignancy has become one of the most consistent epidemiologic findings for this disease in recent years. Well over a dozen studies, both case-control and cohort, employing several different methods of physical activity assessment, have demonstrated this association (Lee et al, 1991). The association with colorectal cancer has been noted for both occupational and leisure-time activity. The extent to which genetic factors, in isolation or in interaction with environmental factors, play a role in sporadic cancers is unresolved. Family history of colorectal cancer in a first-degree relative has been estimated to confer approximately a three-fold risk of this malignancy. Analyses of kindreds in Utah have been interpreted to indicate a dominant pattern of inheritance for susceptibility to adenomatous polyps and colorectal cancer (Cannon-Albright et al., 1988). Investigators have recently identified mutated genes involved in the development of familial adenomatous polyposis (FAP) (Groden et al., 1991), a rare inherited condition that is characterized by many hundreds of large intestinal polyps and progresses to cancer with a very high frequency, and hereditary nonpolyposis colon cancer (HNPCC)(Leach et al., 1993), a familial syndrome in which affected individuals develop tumors of the colon (and other organs) often before 50 years of age. Scientists are continuing to explore genetic defects that may be involved in the development and progression of colorectal cancer. Large bowel cancer mortality rates have declined for white men and women in the United States in recent years. Investigators have recently presented evidence linking this decline to improved early detection procedures (Chu et al., 1994). The increased use of sigmoidoscopy and fecal occult blood tests (followed by colonoscopy) may have played an important role in reducing mortality from large bowel cancer.
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