Environmental factors of cancer of the colon and rectum

Wynder, Ernest L.; Shigematsu, Takao

doi:10.1002/1097-0142(196709)20:9<1520::aid-cncr2820200920>3.0.co;2-3

Cited by 473 publications

(102 citation statements)

References 94 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: 88%

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: 88%

Free radicals and the etiology of colon cancer

Babbs

1990

Free Radical Biology and Medicine

313

174

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“…Currently it is assumed that dietary factors modulate a genetic susceptibility. In epidemiolog ical observations, the consumption of animal fat is positively related to the incidence of colon cancer [1,2]. The intake of fibre is possibly negatively related to this incidence; however, many inconsistencies exist [3].…”

Section: The Role O F Dietary Factors In Colonic Carcinogenesismentioning

confidence: 99%

Role of bile acids in colorectal carcinogenesis

Nagengast

Grubben

Munster

1995

European Journal of Cancer

316

180

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Dietary factors are considered important environmental risk determinants for colorectal cancer development. Epidemiological studies have shown that a high fat (or meat) intake is associated positively and a high starch, fibre (non-starch polysaccharide), vegetable and fruit intake negatively with colorectal cancer incidence. One mechanism by which these effects are possibly exerted is through the metabolism of secondary bile acids. Secondary bile acids are formed after enzymatic deconjugation and dehydroxylation of primary bile acids in the large bowel by anaerobic bacteria. It has been shown that these compounds can have tumour-promoting capacities in animal experiments. In epidemiological studies, colonic cancer risk is related to the faecal bile acid concentration. In serum and bile of patients with colonic adenomas, more deoxycholic acid was detected than in healthy controls. Secondary bile acids are toxic to several cell systems at physiological concentrations. The exact mechanism by which these amphiphilic molecules exert their action is not well understood. It might act through membrane damage, intracellular mitochondrial action or genotoxic effects. So far the evidence that bile acids are involved in colonic carcinogenesis is largely circumstantial. It is, however, well accepted that environmental factors, such as dietary habits influence genetic susceptibility. Bile acids could play a promoting role in this process.

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“…Mortality for colorectal cancer (CRC) and for myocardial infarction (MI) are associated at population level [39]. Correa et al [7] found in an autopsy study on 842 autopsies, that the most extensive atherosclerotic involvement of the aorta was in subjects with adenomatous polyps of the colon, and even more in subjects with adenonomatous and hyperplastic polyps together.…”

Section: Introductionmentioning

confidence: 99%

Nutrition, metabolism and colorectal cancer

Misciagna

Caruso

Trevisan³

2008

Genes Nutr

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Colorectal cancer and myocardial infarction are associated at population level and in autoptic studies. Furthermore, they share many blood variables: cholesterol, triglycerides and HDL cholesterol, fructosamine, glycated haemoglobin and glycated apolipoprotein B. These blood variables are intermediates between dietary, mainly saturated fats and high glycemic index and load diets, and colorectal cancer and myocardial infarction. Blood intermediate variables can be used in dietary trials as outcomes, and even to throw light on the pathogenesis of both diseases.

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Environmental factors of cancer of the colon and rectum

Cited by 473 publications

References 94 publications

Free radicals and the etiology of colon cancer

Free radicals and the etiology of colon cancer

Role of bile acids in colorectal carcinogenesis

Nutrition, metabolism and colorectal cancer

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