Colorectal cancer (CRC) is the third most prevalent tumor worldwide after lung and breast cancer. According to the Global Oncology Epidemiology Statistics (GLOBOCAN), about 600,000 people die from CRC worldwide every year, making it the fourth deadliest tumor in the world. CRC has become one of the major malignant tumors endangering the health of Chinese residents, which has brought a heavy burden to the social economy and medical care in the past 40 years, with the rapid economic progress, changes in national living habits and dietary structure, and accelerated aging process.
Colorectal cancer is mostly disseminated, among which 70%-90% of colorectal cancer is related to dietary factors. Numerous epidemiological and etiological studies on migration have concluded that the difference in the incidence of colorectal cancer between the East and the West is mainly due to dietary and nutritional factors. Therefore, dietary optimization will be beneficial to prevent and treat most colorectal cancers.
I. Red meat and meat products
The role of red meat and meat products in the development of CRC is well established. a 2011 meta-analysis pooling all prospective cohort studies from 1966 to March 2011 showed that red meat and meat products elevated the risk of CRC and that there was a dose effect, i.e., each 100 g/d increase in red meat intake increased the risk of CRC by 29%, while each 50 g/d increase in meat product intake increased the risk of CRC by 21%. The association was particularly pronounced in men. Therefore, the World Cancer Research Fund-American Institute for Cancer Research (WCRF-AICR) recommends that red meat consumption should not exceed 500g per week and that cured and smoked meats should be avoided. The causes of CRC from meat can be broadly attributed to the following factors.
1. Animal-derived fat
A large study involving 130,000 people showed that a low intake of animal-derived fat reduced the risk of CRC by 20%. At the same time, there may be a dose effect between animal-derived fat intake and CRC incidence. It has also been reported in China that fat intake was significantly higher in the colon cancer group than in the control group, and that high fat intake significantly increased the risk of CRC after adjusting for the effects of suspected confounding factors. The carcinogenic effect of saturated fat may be produced through fatty acids and other oxidation products. Increased fat intake leads to increased production of cholesterol and bile acids, both of which enter the lumen of the large intestine where anaerobic bacteria-dominated colonic flora can transform them into metabolites such as oxidized bile acids, which are converted to carcinogens in vivo, such as deoxycholic and lithocholic acids, thereby producing cytotoxic effects on epithelial cells of the colonic crypt and causing irreparable DNA damage. Fatty acids, especially in their ionic state, can induce an inflammatory response in the intestine by producing prostaglandin E2, induce and activate ornithine decarboxylase, and alter the composition of intestinal flora, making ingested fat more susceptible to the formation of oxidized carcinogens such as deoxycholic acid, and can cause nonspecific damage to the colonic mucosa and epithelial cell proliferation, inducing CRC. fat metabolism may also produce free amines and phenols, damaging the intestinal mucosa However, the relationship between the above substances and CRC is not yet supported by clear evidence. In addition to saturated fatty acids, a high-fat diet can lead to obesity, which leads to insulin resistance and many changes in blood composition. Diabetes and obesity are independent risk factors for the development of CRC.
2.Hemoglobin
Many epidemiological and animal studies have shown that increased intake of ferrous hemoglobin in red meat will increase the probability of developing colon cancer. The possible mechanism is that ferrous hemoglobin produces hydrogen peroxide through heme oxygenase, which triggers DNA damage and abnormal proliferation of colonic epithelial cells. In addition, hemoglobin can enhance the damaging effects of fatty acids themselves and nitroso by producing heme.
3.Toxic substances
Red meat and meat products are rich in nitroso compounds, which can cause damage to DNA, and red meat cooked at high temperature can produce a large number of heterocyclic amino acids that can cause cell mutation, which can also change the normal synthesis and secretion of bile acids and change the distribution of intestinal flora, resulting in an environment prone to tumor growth.
II. Fiber and total carbohydrates
WCRF-AICR has formally recognized fiber as an influencing factor for the occurrence of CRC, and concluded that consuming 10g of dietary fiber per day would reduce the incidence of CRC by 10%. Large European epidemiological studies have shown that dietary fiber intake is negatively associated with the development of colorectal cancer and is independent of the source of dietary fiber. Dietary fiber can increase the frequency and volume of bowel movements and bind to certain macronutrients, thus reducing the contact time and exposure of the intestinal lumen to carcinogens while decreasing the time of stool accumulation.
At the same time, fiber increases key enzymes in the beta-oxidation and direct lipid production pathways, such as triglyceride lipase, acetyl coenzyme A carboxylase, and fatty acid synthase, thereby lowering blood lipids, reducing cholesterol synthesis and increasing cholesterol excretion in bile. Fiber also plays a positive role in the immune system and inflammation control, and modifies the intestinal flora, altering host metabolism in many ways, including increased dissociation of bile acids and production of more short-chain fatty acids.
It has to be noted, however, that fiber-rich fruits, vegetables and legumes are often accompanied by a variety of other possible carcinogenic substances, which may influence the results of studies on a single factor of fiber. In addition, different types and sources of fiber may have different effects. There is no uniform conclusion on whether total carbohydrate is a risk factor for CRC development. The uncertainty of the study results may be related to the type and intake of carbohydrate, and it is uncertain whether different types of carbohydrate have different effects on the incidence of CRC. In addition, carbohydrates may elevate blood glucose and blood C-peptide levels, and thus may increase the incidence of colorectal cancer.
Drink
1.Drinking alcohol
A number of observational studies have shown that excessive alcohol consumption will significantly increase the incidence of CRC, and the correlation is stronger in men. A meta-analysis showed that moderate drinking (>1-4 drinks/d) and heavy drinking (>4 drinks/d) would increase the incidence of CRC by 21% and 52%, respectively, compared to non-drinkers or occasional drinkers; while in women, moderate drinking only increased the incidence of CRC by 8%. This may be related to differences in mean alcohol consumption between the sexes, and may also be due to real differences in alcohol metabolism between men and women.
Alcohol-induced CRC formation may lend itself to the following pathways.
(1) Ethanol is first oxidized to acetaldehyde, which results in the formation of some DNA adducts and leads to genotoxicity.
(2) Prolonged exposure to alcohol increases the level of reactive oxidation products in the body, which inhibit detoxification-related enzymes and generate secondary oxidation reactive products through other pathways, which act on DNA and key proteins.
(3) Ethanol metabolism depletes the body of tetrahydrofolate, and excess alcohol leads to cellular hypomethylation. It can be said that alcohol and CRC incidence are influenced by the methyl donor content of food. The hypothesis that alcohol causes tumorigenesis through epigenetic alterations is supported by the fact that a high alcohol intake accompanied by a hypomethyl diet is more likely to develop CRC than a high alcohol intake population alone. However, there is a lack of studies in which methyl donor, gender and alcohol intake are combined risk factors.
2. Dairy products and calcium
Milk is thought to reduce the incidence of CRC, mainly colon cancer. A recent meta-analysis showed that the RR of colon cancer in people who consumed 4009 dairy products per day was 0.83 (95% CI: 0.78-0.88). These effects were present in both men and women. There was a non-linear negative association between milk intake and colon cancer incidence and the protective effect was most pronounced in the highest intake group. The protective effect of dairy products was mainly through calcium. In a recent meta-analysis of three randomized cohort studies, Carroll et al. found that a daily intake of 1200-2000 mg of calcium, with or without other micronutrients, reduced the risk of colorectal adenoma by 20% in patients with a history of colorectal polyps. The study also showed that calcium intake delayed adenoma development. However, in people without additional risk of CRC, there was no evidence that calcium supplementation provided a significant benefit: this may also be related to the fact that people at low risk tend not to be deficient in calcium themselves.
It is currently hypothesized that the protective role of calcium in the development of CRC can be attributed to the following sources.
(1) the ability of calcium to bind to secondary bile acids as well as ionized fatty acids, forming inert material that reduces the contact of the latter two with the intestinal lumen and acts as an anti-inflammatory agent.
(2) Direct action on the cell cycle, reducing cell proliferation, promoting cell differentiation, and promoting apoptosis in heterogeneous cells. In conclusion, people with low calcium intake and those at high risk for CRC should increase calcium intake by consuming dairy products with low saturated fatty acid content, such as low-fat milk, cheese or yogurt.
3. Coffee
Coffee can reduce the risk of CRC, but the strength of its effect varies widely among the available findings. One study showed that only when adjusted for smoking and alcohol consumption factors, coffee had a weak protective effect in women who drank more than 4 cups per day; while another report showed that coffee was significantly negatively associated with the occurrence of CRC. Caffeine is generally considered to be the key substance in the preventive effect of CRC. It interacts with anti-tumor cytokines in the body, which can inhibit tumor cell DNA synthesis, inhibit potentially lethal DNA repair, release G2 blockade, etc., and thus reduce tumor incidence. The chlorogenic acid and digestive fiber (including black extract-like) in coffee can increase colonic dynamics and maintain the antioxidant status of the intestinal lumen. Combined with other related substances, coffee can prevent cell mutation, antioxidant, reduce the secretion of bile acids into the colon, and eliminate many carcinogens through caffeol and coffee white ester. Coffee can also affect intestinal functions, such as changing intestinal flora, defecation habits, and maintaining a reductive environment in the intestinal lumen.
IV. Vitamins and micronutrients
1.Vitamin D
In areas with high latitude and relatively low vitamin D level, colorectal cancer is often high, which confirms the preventive effect of vitamin D on CRC. Vitamin D can play an anti-proliferation and differentiation role through cell signaling pathways and gene transcriptional mediation. There is a general consensus on the preventive effect of vitamin D on CRC, but there is still a lack of data to support the optimal dose of supplementation. More studies are needed to further explore the effects of vitamin D.
2. Folic acid
The protective effect of folic acid was first identified in a large prospective cohort study. Based on the results of the current study, it appears that only folic acid in food is associated with colorectal tumors, and there is not enough evidence from the relevant studies. In addition, the effects of folate are associated with other methyl donors (e.g., methionine) and methyl depleting substances (e.g., alcohol). Therefore, the separate effects of folic acid are often difficult to study. Both folates and folic acid are converted in endogenous metabolism to 5-methyltetrahydrofolate, which enters the one-carbon cycle and serves as the major methyl donor for DNA nucleotide synthesis. hypermethylation or hypomethylation of DNA are both early markers of cancer development. When folic acid intake is inadequate, mismatch of uracil, DNA misrepair and epigenetic variants (e.g. hypomethylation) are likely to occur, triggering DNA damage that can lead to colorectal carcinogenesis. A recent analysis has shown that consuming above-average amounts of dietary folic acid reduces the risk of CRC by 8%. However, three meta-analyses based on randomized controlled trials have also shown that folic acid supplementation is not protective against colorectal adenomas, and there is even evidence that folic acid may lead to neoplastic formation.
Therefore, it has been hypothesized that folate has different roles in different stages of tumor formation: deficiency in the early stages increases the risk of cancer formation, while excess folate instead contributes to abnormal proliferation when it enters the progressive stage. Due to the possible dual role of folic acid, it becomes worthwhile to explore at what age and in what state to start supplementing folic acid.
3. Selenium
Selenium intake is negatively correlated with the death rate of colon cancer. According to the analysis of three randomized controlled trials, the highest selenium intake group can reduce the incidence of colorectal polyps by 33% compared to the lowest intake group. Selenium enters the body to form a specific protein containing selenocysteine (Sec), SEP, which is thought to be associated with the antitumor effects of selenium.SEP is able to protect DNA from oxidative damage by activating P53, enhancing its gene repair function, inducing apoptosis, and playing a role in both the immune system and insulin signaling.The redox capacity of SEP also allows it to play a role in the development of inflammation, especially in the cyclooxygenase 2 pathway. In particular, it plays an important signaling role in the cyclooxygenase 2 pathway. However, there are side effects associated with selenium administration, including an increased incidence of diabetes. Therefore, selenium supplementation is not currently advocated in people who are not deficient in selenium.
V. Fish diet
The correlation between the high intake of fish and the occurrence of CRC has been the subject of mixed findings in previous studies. Fish is rich in vitamin D3 and n-3 unsaturated fatty acids (PUFAs) with anti-inflammatory effects, both of which have been shown to prevent colorectal cancer in laboratory studies. A recent meta-analysis including 22 prospective studies and 19 case-control studies showed that high fish consumption reduced the overall risk of CRC by 12% (OR: 0.88, 95% CI: O.8-0.95), but the confidence and strength of the results were weakened when only prospective studies were counted. Thus, fish diet may be associated with CRC occurrence, but more evidence is needed to support its relevance.
VI. Polyphenols and others
Polyphenols are commonly found in fruits and vegetables and in beverages such as green tea. These compounds can act on a variety of cell cycle-specific proteins, mainly acting on G1/s and G2/M regulatory sites leading to cell cycle capture and apoptosis, thus regulating cell growth; they can inhibit proliferation via nuclear transcription factor (NF)-KB, GFR/Ras/MAPK and other pathways without cytotoxicity, and also prevent tumor-associated neovascularization as well as tumor In addition, the presence of hydroxyl groups in polyphenols makes them have anti-inflammatory and antioxidant effects. The effects of polyphenols have been mainly studied in in vitro cell lines of CRC, but have not been confirmed in human trials. In addition, any food or nutrient that may be associated with inflammatory pathways may be associated with the development of CRC. For example, turmeric in Indian curries and anthocyanin-like compounds in blue and red fruits have been reported to be possibly associated with CRC prevention.