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    Colorectal Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Description of the Evidence

    Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs continued...

    A central effect of bile acids in the etiology and pathogenesis of CRC has been claimed.[109] An increased bile acid concentration in the intestinal tract accompanies a high-fat diet because bile acids are released from the gallbladder after fat ingestion. The concentration of bile acids in the colon is heavily influenced by the amount and type of fat in the diet.[110] The potential mechanism of action of bile salts in colorectal carcinogenesis is unknown, although it has been suggested that it is mediated by diacylglycerol.[111] The conversion of dietary phospholipids to diacylglycerol by intestinal bacteria is enhanced by a high-fat diet. It is proposed that diacylglycerol enters the cell directly, stimulating protein kinase C, which is involved in intracellular signal transduction. There is no high-quality evidence from either observational studies or RCTs to substantiate this claim.

    Dietary fiber, vegetables, and fruit

    The evidence on whether dietary fiber exerts a protective role in reducing the incidence of CRC is mixed. Most animal and epidemiologic studies show a protective effect of dietary fiber on colon carcinogenesis.[51] The term fiber is used to describe a complex mixture of compounds, including insoluble fiber (typified by wheat bran and cellulose) and soluble fiber (usually dried beans). Ingestion of fiber could modify carcinogenesis in the large bowel by a number of potential mechanisms.[112,113,114] These mechanisms include binding to bile acids, increasing fecal water and possibly diluting carcinogens, and decreasing transit time (not an obvious factor). Fiber may act as a substrate for bacterial fermentation with a resultant increase in bacterial mass and the production of short-chain fatty acids, typified by butyrate.[114] Butyrate has been shown to have anticarcinogenic effects in vitro and is regarded as an important fuel for the colonic epithelium.[115,116] A meta-analysis of 13 case-control studies from nine countries concluded that intake of fiber-rich foods is inversely related to cancers of both the colon and rectum.[117] The analysis did not include fiber supplements. The inverse association with fiber was observed in 12 of the 13 studies and was similar in magnitude for left-sided and right-sided colon and rectal cancers, in men and women, and in different age groups. It has been suggested that the inverse association with fiber may be reflective of some other closely associated dietary constituents, such as the anticarcinogens found in vegetables, fruits, legumes, nuts, and grains.[10,117] These substances include phenolic compounds, sulfur-containing compounds, and flavones.[118,119] In a prospective cohort study of a low-risk population, an inverse association was found with legume intake and the risk of CRC (RR for >2 times/week vs. 1 time/week = 0.53 [95% CI, 0.33-0.86; P for trend = .03]).[98]

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