Fatal Colorectal Cancer Research Articles

Aspirin, age, and proximity to lymphoid nodules influence cell proliferation parameters in rat colonic crypts

Recent epidemiological studies have demonstrated a correlation between regular aspirin (acetylsalicylic acid) use and decrease risk for the development of fatal colorectal cancer. An increase in the size of the cell proliferation compartment in colorectal crypts has been correlated with an increased risk for the development of colon cancer in animals and in humans. To determine if acetylsalicylic acid acts to decrease the size of the cell proliferation compartment, young (3 month) and old (22 month) rats were treated intragastrically with: 1 the vehicle for acetylsalicylic acid delivery (0.25% wt/vol carboxymetylcellulose in 0.15 N (HCl), 2 a single dose of acetylsalicylic acid (100 mg/kg), or 3 acetylsalicylic acid (30 mg/kg) given daily for 30 days. One day after the last treatment, colons were resected, fixed, sectioned and mounted on slides for immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen to assess cell proliferation parameters in the colonic crypts. The results were subjected to three way analysis of variance to assess the effects of: 1 rat age, 2 acute or chronic acetylsalicylic acid treatment, and 3 location of crypts over and away from aggregates of lymphoid nodules on the crypt proliferative parameters. Results demonstrated that: 1 acetylsalicylic acid treatment caused on overall decrease in the proliferative zone height, as measured in number of cells in the crypt column, 2 that crypts located over aggregates of lymphoid nodules had significantly higher proliferative activity than crypts located away from aggregates of lymphoid nodules, and 3 after chronic acetylsalicylic acid treatment there was a greater suppression of proliferative zone height in the crypts of old rats than in the crypts of young rats. In conclusion, acute and chronic intragastric delivery of acetylsalicylic acid caused an overall downward shift in the cell proliferation compartment of colonic crypts of young and of old rats. Whether or not acetylsalicylic acid administration will cause the same proliferative zone height response in carcinogen-treated rats is not yet established.

Effect of fecal occult blood testing on mortality from colorectal cancer. A case-control study.

To estimate by case-control methods the effect of screening using the fecal occult blood test (FOBT) on mortality from colorectal cancer and to examine the relation of that effect to the interval since the most recent screening test. A case-control study. The Kaiser Permanente Medical Care Program of Northern California. A total of 485 persons who developed fatal colorectal cancer after 50 years of age and 727 age- and sex-matched controls. History of screening FOBTs during the 5 years before case diagnosis. After adjustment for potentially confounding factors, an odds ratio of 0.69 (95% Cl, 0.52 to 0.91) was observed for exposure to at least one screening FOBT during the 5-year interval. The odds ratio was lowest for the first year after the most recent FOBT and rose to 1.00 three years after the last screening examination. False-negative results among cases in the 1 to 2 years before diagnosis contributed substantially to lowering the estimate of efficacy. These data suggest that a program of annual or biennial screening using FOBTs might lower population risk for mortality from colorectal cancer sufficiently to have important public health implications. However, the confidence intervals around our odds ratio estimates were wide. We therefore believe that additional data will be needed before making recommendations that FOBT screening be expanded.

An International Search for Causative Factors of Colorectal Cancer

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.

Dietary Relationships With Fatal Colorectal Cancer Among Seventh-Day Adventists<xref ref-type="fn" rid="FN2">2</xref>

Associations between fatal colon or colorectal cancer and frequency of use of meat, cheese, milk, eggs, green salad, and coffee, as well as percent desirable weight, are described with the use of 21 years of follow-up for 25,493 white California Seventh-Day Adventists. Associations are presented in terms of relative risk (RR) of colorectal cancer for heavy or light exposure versus rare exposure. There were no clear relationships evident between colon or rectal cancer and meat, cheese, milk, or green salad use. Egg use was positively associated with risk of fatal colon cancer in both males (RR = 1.6) and females (RR = 1.7). Coffee use was positively associated with both colon and rectal cancer mortality in males and females, particularly for colon cancer during the last 11 years of follow-up (male RR = 3.5; female RR = 1.9). Overweight (percent of desirable weight greater than or equal to 125) was associated with an increased risk of fatal rectal cancer in both sexes combined (RR = 2.8) and colon cancer in males only (RR = 3.3). Furthermore, eggs, coffee, and overweight appear to be independently associated with risk of both colon and colorectal cancer. These three factors may explain a substantial portion of the colorectal cancer mortality differential between Adventists and U.S. whites (62% for males; 30% for females).