Colorectal cancer is one of the major cancers in the world, and its incidence rate varies greatly, between 10 to 20 times. In economically developed regions such as North America, Western Europe and Australia, the incidence can be as high as 25-35 cases per 100,000 people, while in India it is the lowest, 1 to 3 cases per 100,000 people. The incidence rate in developing countries has gradually increased in recent years. The risk of colorectal cancer increases to the level of high incidence areas for second generation immigrants who migrate from low incidence areas to high incidence areas, which may be the result of the influence of lifestyle and environmental factors. The close relationship between dietary and environmental factors and colorectal cancer suggests that the risk of colorectal cancer can be reduced through proper dietary structure and dietary nutrition, and may play an important supporting role in the comprehensive treatment of colorectal cancer.
A large amount of epidemiological evidence shows that dietary structure and certain special dietary habits are closely related to the occurrence of colorectal tumors.
High-fat and high-cholesterol diet
Epidemiological data show that high-fat and high-cholesterol diet can significantly increase the incidence of colorectal cancer. If bile acid and cholesterol were added together, the cancer-inducing effect of DMH was significantly increased, and the cholesterol-free diet significantly increased the survival time of DMH-induced colorectal cancer animals and significantly reduced the metastasis rate of tumors
Bile acids are essential for fat absorption, and the carcinogenic effect of fat may be mediated by bile acids. A high-fat diet can stimulate the secretion and excretion of bile acids and biliary homo-ol, and promote the development of colorectal cancer. Some scholars have conducted qualitative and quantitative analyses of fecal bile acids and neutral cholesterol in high-risk and low-risk groups of colorectal cancer patients with different diets, and pointed out that the increased excretion of fecal bile acids and neutral sterols in high-fat diet was significantly associated with the high incidence of colorectal cancer, and the group of colorectal cancer patients had higher concentrations of fecal bile acids and cholesterol metabolites than the control group. The excretion of fecal bile acids was higher in healthy youths on a high-fat diet than on a low-fat diet, and high-fat diet in rats not only increased the excretion of fecal bile acids and neutral cholesterol, but also promoted chemical carcinogenesis.
In addition, increased secretion of bile acids into the intestine can affect the composition of the intestinal microflora, and intestinal bacteria in the large intestine can metabolize acidic and neutral cholesterol into co-carcinogens or carcinogens, stimulate secondary bile acid production and promote the occurrence of colon cancer. immune status of the body; altered enzyme systems involved in the metabolism of carcinogens. Increased fat consumption leads to increased bile acids in the colonic intestinal lumen. Bile acids in the feces have a direct damaging effect on epithelial cells and promote the proliferation of epithelial cells in animals and humans.
Low-fiber diet
Epidemiological surveys have shown that the incidence of colorectal cancer is low in Africans on a high-fiber diet and high in Americans on a low-fiber diet. A high-fiber diet significantly inhibits the carcinogenic effect of azomethine (AOM) on the colon, and as the amount of dietary fiber increases, the fecal volume of animals increases, while the incidence of DMH-induced colorectal cancer decreases. Fiber can bind to DMH with each other, and certain types of fiber can counteract chemical-induced colorectal cancer, which is partly due to increased binding of carcinogens to dietary fiber in the colon. In addition, certain dietary fibers such as gum and carob can reduce serum cholesterol and bile acids and neutral sterols in feces.
Anti-cancer mechanisms of dietary fiber.
1.Reducing the concentration of carcinogenic substances in the large intestine.
2.Shorten the passage time of toxins in the intestinal lumen, thus reducing the contact between carcinogenic substances and tissues.
3.Reducing the production of certain carcinogenic substances or pre-carcinogenic substances.
4.Regulating effect on endocrine system.
5.Changes in bile acid metabolism and increased production of short-chain fatty acids.
Trace elements
Selenium is an essential nutrient for human health, and may have an anti-tumor effect. Epidemiological survey shows that the blood selenium level in urban residents of the United States is negatively correlated with the total tumor incidence in the population, although the blood selenium level may be affected by the disease process, but some studies have shown that selenium can inhibit the occurrence of cancer, and the occurrence of intestinal cancer in selenium-deficient areas is significantly higher; many animal experiments have shown that selenium supplementation to animals can significantly inhibit the carcinogenic effect of chemicals on the colon; foreign scholars such as Jacobs found that inorganic selenium can inhibit the occurrence of experimental colorectal cancer caused by DMH, and domestic Yu Baoming obtained the same result by applying organic selenium – selenium yeast. The anti-colon tumor effect of organic germanium has also been reported.
The anti-cancer mechanisms concerning selenium may be.
1, selenium can change the metabolism and detoxification of carcinogenic agents, which can inhibit the oxidation process such as DMH and lipid peroxidation by inhibiting glutathione peroxidase, thus maintaining the soundness of cell membrane structure and function and preventing the damage to DNA.
2.Selenium improves the activity of glutathione S-transferase, which reduces the electronophilic sensitivity of carcinogens such as DMH, thus reducing the occurrence of tumors.
3.Increasing the blood selenium level of colorectal cancer patients can improve their immune status and antioxidant function of the body. Experimental research has found that increasing the dietary selenium content can improve the potency of anti-sheep red blood cell IgM and IgG antibodies.
4.It can stimulate DNA repair and prevent DNA alkylation.
Multivitamins, folic acid
Mechanism of vitamin anti-tumor.
1.Antioxidation and scavenging free radicals.
2.Enhance immune function.
3.Change the nature of chemical carcinogens and block their propagation.
4.Increase the traffic of intercellular junctions.
5.Maintain cellular DNA methylation status.
Vitamin D
The literature shows that higher intake of vitamin D through diet or other means can reduce the incidence of colorectal tumors, long-term VitD deficiency can promote the occurrence of colon cancer, and high vitD intake is significantly associated with the reduction of precancerous lesions in the colonic mucosa. The data from nine regional cancer registries in the United States confirm that sun exposure is beneficial in reducing rectal cancer incidence, thus providing indirect evidence for the anti-colon tumorigenic effects of vitamin D. Overall experiments found that 1,25(OH)2D3 inhibited DMH-induced colon tumorigenesis in rats; ex vivo experiments showed that dihydroxy D3 significantly inhibited proliferation of cultured rectal epithelial cells, while VitD and its derivatives significantly inhibited the growth of human colon cancer cell line HT-29. All these studies suggest that vitamin D is an important factor in preventing malignancy of colonic epithelial cells and regulating their growth and differentiation. The mechanism of action of vitamin D on colorectal tumors.
1, mediated through intracellular vitamin D receptor (VDR).
2, via non-VDR pathway, protein kinase C action, PKC is involved in a series of processes such as growth, differentiation and cell proliferation of colon tumor cells, and its activation is related to the activation of c-myc and Fas genes; in addition, experiments have shown that VitD can regulate the frequency of K-ras gene mutation in DMH rat colonic epithelial cells, which can increase DNA by reducing K-ras DNA methylation adduct repair-associated protein activity to inhibit the effect of carcinogens.
Vitamin A and lipophilic factor deficiency
Reduced dietary lipophilic factors methionine and choline can alter the metabolism of intestinal carcinogens in the liver. It has been shown that diets high in lipids without choline and methionine or VitA can increase the carcinogenic effects of chemicals on the colon. Administration of a high VitA diet to animals significantly inhibited the carcinogenic effects of DMH, aflatoxin B. However, the opposite conclusion has also been made that VitA deficiency reduces the carcinogenic effect of MNNG and inhibits the development of colorectal cancer.
Folic acid
Low folic acid intake can lead to reduced DNA methylation, resulting in abnormal DNA synthesis and repair, thus promoting colon carcinogenesis. Prospective studies have shown that folate deficiency increases the risk of colon cancer and that high dietary folate intake and long-term folate supplementation may reduce the risk of colon cancer. Both case-control and cohort studies suggest that high vegetable intake is associated with a reduced risk of colorectal cancer, but the nutrients involved are unknown. evidence from Giovamoucci et al. suggests that folate intake is negatively associated with colon cancer. The relative risk of colon cancer was 0.9 for those consuming 201-300 μg/day, 0.8 for those consuming 301-400 μg/day, and 0.7 for those consuming >400 μg/day compared to women consuming ≤200 μg/day of folic acid. in the highest intake group, 86.3% was multivitamin supplementation, with the remaining three groups coming primarily from diet. When corrected for the presence of other nutrients in the multivitamins, the negative association between folic acid intake and colon carcinogenesis remained. Analysis of the duration of administration of folic acid-containing multivitamins showed that the negative association was not evident until at least 5 years of administration, with the most significant effect occurring after at least 15 years of administration.
Intestinal flora
Studies have confirmed that
1, in the stool of patients with colorectal cancer and colorectal polyps, bacteria can convert primary bile acids into secondary bile acids, and the latter has a significant pro-cancer effect in animal experiments.
2. DMH can induce colorectal tumors in normal rats with a cancer-inducing rate of 93%, but only 20% in germ-free rats, and the use of inhibitors of bacterial glucosidase can significantly reduce the number of AOM-induced tumors. Both experiments indicate that intestinal bacteria and their enzymes can activate the metabolism of indirect carcinogens DMH and AOM, which play a role in the occurrence of colorectal cancer.
3. Glucosidase activity was significantly elevated in the stool of high-risk diet population, and the high activity of this enzyme can promote the conversion of glucuronides to carcinogenic ligands. Many toxic substances in the body, including carcinogens, are detoxified in the liver and excreted into the intestine with bile in the form of 6-monoglucuronide, which can be re-liberated and act under the action of this enzyme.
4, rats from cereal to meat diet, the fecal nitro reductase and azo reductase significantly increased. These two enzymes can reduce nitro and azo compounds to aromatic amines. In the reduction process can form nitro and N a hydroxyl compounds. Nitrite and secondary or tertiary amines form nitrosamines in a suitable acidic environment in the mammalian stomach. These compounds can be converted into calloused substances under the action of intestinal bacteria. Several hydrazines and DMH have been successfully induced in animals for the development of colorectal cancer, and these compounds are well-known carcinogens.
5. In the stools of colorectal cancer patients and high-risk groups, anaerobic bacteria are significantly increased, especially Clostridium difficile. The latter can desaturate bile acid nuclei, producing unsaturated cholesterol and forming polycyclic aromatic hydrocarbons.
6. Mutagenic substances have been found in human stool for Salmonella typhimurium FA98 and TAl00, and their mutagenicity is higher in high-risk groups of colorectal cancer than in low-risk groups. If the feces is incubated with anaerobic bacteria, the mutagenic substances can be increased 20 times.
7.Clinical experiments have proved that Rejuveno has the effect of improving the immune function of colorectal cancer patients, and this improvement of systemic immune function may be related to the anti-tumor effect of Rejuveno.
In addition, WPG activates the immune effector cells such as macrophages, NK cells and B lymphocytes in the immune system, which secrete a large amount of cytotoxic effector molecules with tumor-killing activity, such as IL-1, IL-6, TNF-α, IFN-γ, NO and various antibodies, etc. It also participates in the tumor suppression mechanism.
9.After Bifidobacterium bifidum injection, the density of PCNA-positive cells in transplanted tumor cells of colorectal cancer nude mice was significantly lower than that of the control group, suggesting that Bifidobacterium bifidum could reduce the proliferation activity of transplanted tumor cells of colorectal cancer and slow their growth.
10, The colorectal tumor induction rate of DMH in normal rats on high-fat diet was significantly higher than that in germ-free rats on high-fat diet and normal rats on low-fat diet, while there was no difference in tumor induction rate of DMH between germ-free rats on high-fat and low-fat diet, which clearly illustrated the relationship between intestinal flora and colorectal cancer.
Heterocyclic amines
Experimental studies for 20 years have emphasized that heterocyclic amines formed during cooking of meat and fish may be associated with the development of human carcinomas. However, recent studies have shown that the level of heterocyclic amines in the general diet is unlikely to increase the incidence of colorectal cancer, and although the risk of cancer is increased in those with heterocyclic amine intakes above 1900 ng/day, the general diet rarely has such high intakes; therefore, dietary heterocyclic amines are not a major factor in cancer. Meat and fish may contain carcinogens other than heterocyclic amines, and the latter may play an important role in the development of cancer.
Coffee
Swedish scholars studied the amount of coffee and dietary habits of 61,000 Swedish women aged 40 to 74. After nine years of follow-up, they found no association between coffee drinking and colon cancer, and even drinking large amounts of coffee did not increase the risk of cancer; likewise, coffee had no preventive effect on cancer.
Eating red meat
Pre-test results from a large worldwide study on the effect of diet on carcinogenesis showed that eating red meat (beef and lamb) was associated with colon cancer development. Among 385 colon cancer patients, those who ate meat in the top 25% had a 40% increased risk of cancer, while those who ate vegetables in the top 25% had a 40% reduced risk of cancer.