The prevention of colon cancer

Sherlock, Paul; Lipkin, Martin; Winawer, Sidney J.

doi:10.1016/0002-9343(80)90226-0

Cited by 39 publications

(3 citation statements)

References 61 publications

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“…It is consistent with many established facts of the epidemiology of the disease [79][80][81][82] including increased incidence of colon cancer in people who 1. ingest a high meat diet (which provides more iron), 2. ingest a high fat diet (which provides more procarcinogens and stimulates bile secretion), 3. ingest a low fiber diet (which allows for greater fecal concentration of both iron, procarcinogens, oxidizable lipids, and bile salts), or 4. suffer from chronic ulcerative colitis (which provides peri-mucosal superoxide from activated leukocytes, heme iron from chronic bleeding, and which also may dictate supplementation of the diet with iron to correct for chronic blood loss and consequent iron deficiency anemia).…”

Section: Implications Of the Hypothesissupporting

confidence: 89%

“…The free radical hypothesis is also consistent with the demonstrated decreased incidence of colon cancer in animals fed antioxidants such as vitamin E, vitamin A, butylated hydroxy anisole (BHA), butylated hydroxy toluene (BHT), ascorbic acid, and selenium [79,[83][84][85][86][87][88]. The report [89] of the ability of phytic acid (inositol phosphate), to reduce the number and volume of azoxymethane induced colon tumors, as well as the mitotic activity of colonic crypts in rats, is also explained by the concept of intraluminal Fenton chemistry.…”

Section: Implications Of the Hypothesissupporting

confidence: 66%

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Free radicals and the etiology of colon cancer

Babbs

1990

Free Radical Biology and Medicine

313

174

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This hypothesis paper reviews diverse evidence suggesting that intracolonic production of oxygen radicals may play a role in carcinogenesis. The hypothesis began to evolve when the author made the chance discovery that 1/10,000 dilutions of feces generated detectable quantities of highly reactive hydroxyl radicals (HO). The rate of HO formation, detected using DMSO as a molecular probe, was quite remarkable, corresponding to that which would be produced by over 10,000 rads of gamma irradiation per day, absorbed in the periphery of the fecal mass adjacent to the mucosa. The relatively high concentrations of iron in feces, together with the ability of bile pigments to act as iron chelators that support Fenton chemistry, may very well permit efficient HO generation from superoxide and hydrogen peroxide produced by bacterial metabolism. Such free radical generation in feces could provide a missing link in our understanding of the etiology of colon cancer: the oxidation of procarcinogens either by fecal HO, or by secondary peroxyl radicals (ROO) to form active carcinogens or mitogenic tumor promotors. Intracolonic free radical formation may explain the high incidence of cancer in the colon and rectum, compared to other regions of the GI tract, as well as the observed correlations of a higher incidence of colon cancer with red meat in the diet, which increases stool iron, and with excessive fat in the diet, which may increase the fecal content of procarcinogens and bile pigments. OVERVIEW OF THE HYPOTHESIS AND RELEVANT CHEMICAL MECHANISMSMy intention in this hypothesis paper is to present a new hypothesis suggesting how oxygen derived free radicals, generated in fecal material next to colonic epithelium, may play a significant role in the etiology of colon cancer. This hypothesis derives from an earlier conjecture by Graf and Eaton [1], coupled with the serendipitous discovery in our laboratory that highly reactive HO radicals can be produced abundantly by suspensions of feces under aerobic conditions. As do many other hypotheses for the pathogenic effects of oxygen centered free radicals in biologic systems [2][3][4][5][6], this one also invokes the superoxide driven Fenton reaction:In feces a ready biologic source of superoxide is the respiratory activity of bacteria [7][8][9][10], notably E. coli [11], perhaps together with spontaneous autoxidation of ferrous iron chelates that have been previously reduced by metabolites of the anerobic subpopulation of fecal flora. Another intriguing source of colonic superoxide is the lipoxygenase activity of normal or sloughed colonic epithelial cells [12]. The necessary iron is provided from the diet, since only a small fraction of dietary iron is absorbed in upper GI tract [13,14]. Hydroxyl (HO) radicals so formed within the colon could easily trigger a variety of carcinogenic mechanisms. For example, they could participate in aromatic hydroxylation reactions [15,16] to form carcinogenic products [17]; they could abstract hydrogen atoms from indoles to form radicals t...

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Section: Implications Of the Hypothesissupporting

confidence: 89%

Section: Implications Of the Hypothesissupporting

confidence: 66%

Free radicals and the etiology of colon cancer

Babbs

1990

Free Radical Biology and Medicine

313

174

View full text Add to dashboard Cite

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“…Colon cancer is generally associated with affluence, and a high intake of animal protein and animal fat [38]. Fat could influence the development of colon cancer by changing the proportion of secondary bile acids, which may be cancer promoters, altering the intestinal flora, influencing rates of drug metabolism, and by a number of other mechanisms [38]. Clearly, more research is needed to identify specific dietary items associated widi increased cancer prevalence, and then to determine the effects of removal of these items from the diet.…”

Section: Fatmentioning

confidence: 99%

Nutrition and cancer: state of the art relationship of several nutrients to the development of cancer.

Rivlin¹

1982

Journal of the American College of Nutrition

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Nutrition and cancer interact in a number of important ways and nutritional factors are increasingly recognized as relevant to both the prevention and treatment of cancer. The role of several nutrients in cancer development is considered briefly here. Deficiency of riboflavin (Vitamin B2) prolongs the survival of tumor-bearing animals, but may accelerate carcinogenesis caused by certain agents, as flavin cofactors are involved in drug and carcinogen metabolism. Deficiency of Vitamin A may enhance the development of tumors of epithelial origin, particularly lung. Evidence is accumulating that Vitamin A and/or its precursors, the B-carotenes, may possibly have an effect in chemoprevention of certain of these epithelial cancers both in animals and in man. The consumption of dietary fat among various nations is correlated closely with increased development of cancers of the breast, colon, and prostate, and possibly of other organs. Studies of migrant populations from Japan to the United States show changes in prevalence of stomach and colon cancer in the direction of the native United States population. Sources of nitrites are of concern because of their potential conversion to carcinogenic nitrosamines. Limitation of the delivery of nitrites may be difficult to accomplish so investigators are exploring the blockade of conversion of nitrites to nitrosamines. Nutrition should not be viewed as the sole means of cancer prevention and treatment but rather as a vital component of any treatment plan.

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Sex differences in the changing anatomic distribution of colorectal carcinoma

Vobecký

Leduc

Devroede

1984

Cancer

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The anatomic site distribution of large bowel cancer was studied in 2079 patients between 1967 and 1980. To measure the trend in the localization of the carcinomas, the slope of the regression line of the proportions at each site over the years was computed. The large bowel was divided into five segments: cecum, ascending colon and hepatic flexure, transverse and descending colon, sigmoid and rectosigmoid junction, and rectum. A significant decrease in the proportions of cancer in the sigmoid for both sexes (slope [b] = −0.89; P < 0.001) and an increase of cecal cancer (b = 0.54; P < 0.004) was observed. Sex‐specific results indicated the diminishing proportion of sigmoid cancer in men (b = −1.04; P < 0.004) with an increase in transverse and descending colon cancer proportions (b = 0.52; P = 0.012). In women, a negative slope of ‐‐0.74 was not significant for sigmoid cancer, but cancer of the cecum showed an increase in proportions (b = 0.80; P = 0.01). The age distribution indicated a significant decrease in proportion of men older than 80 years and of women in the age group of 40 to 49 years and an increase in women older than 80 years. However, age adjustment did not change any of the previous conclusions. The observed sex differences in the changing distribution within the large bowel over a 14‐year period cannot be explained by the improvement of diagnostic tools in the last years. In view of these findings, it is important to evaluate the possible sex‐related bias in the application of screening and preventive measures as well as the changes in the ecologic features of the large intestine.

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The prevention of colon cancer

Cited by 39 publications

References 61 publications

Free radicals and the etiology of colon cancer

Free radicals and the etiology of colon cancer

Nutrition and cancer: state of the art relationship of several nutrients to the development of cancer.

Sex differences in the changing anatomic distribution of colorectal carcinoma

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