Colon cancer (mCRC)

Description: Colon cancer is a common malignant tumor of the digestive tract, accounting for the second place in the gastrointestinal tumor. The predilection site is the rectum and the junction of the rectum and the sigmoid colon, accounting for 60%. The incidence is more than 40 years old, the ratio of male to female is 2:1. Etiology: Clinically, certain factors may greatly increase the risk of developing the disease. They include: 1. Age of onset, most patients develop after 50 years of age. 2. Family history: If a person's first-degree relatives, such as parents, have had colorectal cancer, he is 8 times more likely to suffer from this disease than the general population. About a quarter of new-onset people have a family history of colorectal cancer. 3. History of colon disease: Certain colon diseases such as Crohn's disease or ulcerative colitis may increase the chance of developing colorectal cancer. Their risk of colon cancer is 30 times that of ordinary people. 4. Polyps: Most colorectal cancers develop from small precancerous lesions, which are called polyps. Among them, villus-like adenomatous polyps are more likely to develop into cancer, and the chance of cacao becomes about 25%; the malignant rate of tubular adenomatous polyps is 1-5%. 5. Gene characteristics: Some familial tumor syndromes, such as hereditary nonpolyposis colon cancer, can significantly increase the incidence of colorectal cancer. And the onset time is younger. (1) Causes of the disease Some colon cancer epidemiological studies have shown that social development status, lifestyle and dietary structure are closely related to colon cancer, and there are phenomena suggesting that the environment and genetic factors affecting the incidence of colon cancer in different parts and age groups may exist. difference. Environment (especially diet), genetics, physical activity, occupation, etc., are possible etiological factors affecting the incidence of colon cancer. 1. Epidemiological studies on dietary factors show that 70% to 90% of cancers are related to environmental factors and lifestyles, and 40% to 60% of environmental factors are related to diet and nutrition to some extent. Dietary factors in the onset of cancer are considered to be extremely important factors. (1) Mechanism of action of high fat, high protein and low cellulose: It can be summarized as follows: 1 affecting intestinal lipid metabolism, high fat diet increases 7a-dehydroxylation enzyme activity, resulting in increased secondary bile acid formation, and The effect of cellulose is reversed, and by inhibiting reabsorption, dilution and adsorption, and chelation, reducing the deoxycholic acid concentration in the intestine increases the solid phase material in the feces and promotes excretion; some dietary factors (such as calcium ions) can lower the intestines. The levels of ionized fatty acids and free bile acids, both of which have an damaging effect on the intestinal epithelium; inhibit the degradation of intestinal cholesterol. Milk, lactose and galactose have the effect of inhibiting the redox effect of cholane. 2 Cellulose also has the effect of changing the intestinal flora, affecting the structure and function of intestinal mucosa, affecting the growth rate of mucosal epithelial cells, mediating the pH of the intestine, and strengthening the mucosal barrier through mucin to reduce intestinal toxic substances to the intestine. Invasion of the epithelium; 3 high fat and some carbohydrates can increase the activity of intestinal cell enzymes (such as glucuronidase, ornithine dehydrogenase, nitroreductase, azolasin, lipoxygenase, cyclooxygenase) ), promote the production of carcinogens and auxiliary cancers. 4 The effect of biological macromolecular activity. When the cytoplasm is acidified, DNA synthesis is inhibited and the cell cycle is prolonged. (2) Vitamins: Case-control studies have shown that carotene, vitamin B2, vitamin C, and vitamin E are all associated with a reduction in the relative risk of colon cancer, and are dose-response. Vitamin D and calcium have a protective effect. (3) Onion and garlic: The protective effect of onion and garlic on the body has been widely recognized, and the inhibition of tumor growth on this type of food has been confirmed many times in the experiment. Garlic oil can significantly reduce colonic mucosal cell damage caused by dimethyl cholestyramine, and can reduce the colon cancer induction rate of mice by 75%. According to the case-control study, the risk of colon cancer in high-intake garlic foods was 74% in the low-intake group. (4) Salt and preserved food: The relationship between salt content and gastric cancer, colon cancer, and rectal cancer. In the high salt intake group, the relative risk of the three cancers increased, and the case-control study suggested weekly intake. The excess risk of colon cancer in three or more preserved foods was 2.2 times (P<0.01) for less than one time, 2.1 times for left colon cancer, and 1.8 times for right colon cancer. The explanation for this risk factor may be related to the carcinogens produced during the food pickling process, and high salt intake may be a concomitant state. (5) Tea: Tea polyphenols are a strong antioxidant that inhibits the carcinogenic effects of carcinogens. According to the case-control study, the risk of rectal cancer in drinking tea (green tea or black tea) more than 3 times per week was 75% of that of less than one, but not related to the colon cancer group. In the past 10 years, the study suggests that tea drinking has a significant negative correlation with the risk of colon cancer, but there are also reports of the opposite. Because of the small number of studies on the protective effect of tea drinking on colon cancer prevention, it is difficult to evaluate the role of tea drinking in the pathogenesis of human colon cancer. The relationship between coffee and colon cancer is still difficult to determine. (6) Trace elements and minerals: 1 Selenium: The mortality rate of various cancers (including colon cancer) is negatively correlated with local dietary selenium intake and soil selenium content. It is speculated that selenium and potassium are associated with a low risk of colon cancer. However, it is believed that these factors may be just some accompanying factors, and do not directly affect the risk of colon cancer in the population. 2 Calcium: Animal experiments have shown that calcium can improve the toxic effects of deoxycholic acid on intestinal epithelium. Some scholars believe that the increase of the concentration of bile acids and free fatty acids in the intestine can promote the occurrence of colon cancer, and calcium can be combined with them to form insoluble saponified compounds, so that their effects on intestinal epithelial stimulation and toxicity are alleviated. Some epidemiological studies have also suggested that calcium intake can prevent the development of colon cancer. 2. Occupational factors and physical activity Insulated asbestos production workers are more common in colon cancer patients, and animal experiments have shown that swallowing asbestos fibers can penetrate the intestinal mucosa. In addition, the metal industry, cotton yarn or textile industry and leather manufacturing. It has been confirmed that in the production process of plastics, synthetic fibers and rubber, a compound which is often used - acrylonitrile has a role in inducing the stomach, central nervous system and breast tumors, and textile workers exposed to the substance, lung cancer and colon The incidence of cancer is high. Despite this, colon cancer is generally not considered an occupational disease. In the analysis of occupational physical activity, it is found that the risk of colon cancer in long-term or frequent sitting is 1.4 times that of some major physical activity, and it is more closely related to cecal cancer. As a result of case-control studies, moderate-intensity physical activity has a protective effect against colon cancer, especially colon cancer. 3. Genetic factors It is estimated that genetic factors may play an important role in at least 20% to 30% of colon cancer patients, 1% of which are familial polyposis and 5% of hereditary polypoid-free colon cancer syndrome patient. 80% to 100% of patients with hereditary familial polyposis may develop malignant tumors after 59 years of age. In addition, patients with familial colonic polyposis have a majority of left colon cancer, while patients with hereditary nonpolyposis often have right colon cancer. Through the case-control pedigree survey of the whole population (1328 cases of colon cancer probands and 1451 population control families), the results showed that the prevalence of colon cancer in the first-degree relatives of different proband groups was significantly higher than that of the second-degree relatives. The age at diagnosis of colon cancer proband is related to the risk of colon cancer in the first-degree relatives. The younger the proband is, the greater the relative risk of colon cancer in the first-degree relatives of the family. The relative risk is six times that of the >55 age group. Family members (first-degree relatives) with a family history of colon cancer, especially those with a colon cancer age of 40 years or younger, should be given high priority. 4. Disease factors (1) Intestinal inflammation and polyps: chronic intestinal inflammation and polyps, adenomas and patients with extensive ulcerative colitis for more than 10 years: the risk of developing colon cancer is several times higher than that of the general population. Patients with ulcerative colitis with severe dysplasia have a 50% chance of developing colon cancer. Obviously, patients with ulcerative colitis have a higher risk of developing colon cancer than the general population. The data in China suggest that the risk of colon cancer in patients with onset of disease for more than 5 years is 2.6 times higher than that of the general population, but not closely related to rectal cancer. For patients with limited and intermittent lesions, the risk of colon cancer is small. Crohn's disease is also a chronic inflammatory disease that invades the small intestine and sometimes the colon. A growing body of evidence suggests that Crohn's disease is associated with colon and small bowel adenocarcinoma, but to a lesser extent than ulcerative colitis. (2) Schistosomiasis: According to the retrospective investigation of cancer deaths in Zhejiang Province from 1974 to 1976 and the survey data of Chinese malignant tumors from 1975 to 1978 and the Chinese schistosomiasis atlas, the relationship between schistosomiasis endemic areas and colon cancer incidence and mortality was discussed. Relevance. There is a very significant correlation between the incidence of schistosomiasis and the mortality rate of colon cancer in 12 counties and autonomous regions in southern China and 10 counties in Jiaxing, Zhejiang Province. It is suggested that in areas where schistosomiasis is seriously endemic in China, schistosomiasis may be associated with high incidence of colon cancer. However, there is little evidence from epidemiological studies about colon cancer and schistosomiasis. For example, in Jiashan County, Zhejiang Province, which is increasingly controlled by schistosomiasis, the mortality rate of colon cancer and the incidence of schistosomiasis in this area have been the highest in China, and the infection rate of schistosomiasis has decreased significantly. However, according to recent survey results, epidemiological and pathological studies of colon polyp carcinogenesis also suggest that polyp carcinogenesis has nothing to do with the presence or absence of schistosomiasis eggs in polyps. In addition, the results of the colon cancer screening conducted in the above two regions do not support schistosomiasis as a risk factor for colon cancer. In the case-control study, no history of schistosomiasis was found to correlate with colon cancer. (3) cholecystectomy: In recent years, there are more than 20 literatures in China about the relationship between cholecystectomy and colon cancer. Some of these studies have shown that after cholecystectomy can increase the risk of colon cancer, especially proximal colon cancer. Men have an increased risk of colon cancer after cholecystectomy; in contrast, women have a lower risk of developing rectal cancer after the procedure. There are also views that the effect of cholecystectomy on female colon cancer is greater than that of men. It is generally believed that the occurrence of tumors is the result of a combination of factors, and colon cancer is no exception. Colon cancer, as a disease closely related to the lifestyle of Western society, is closely related to its etiology, and it is considered that the role of dietary factors is the most important. The etiology of “high fat, high protein, high calorie and lack of cellulose intake” is still dominant, and most of the results are consistent with this model. Other carcinogenic factors have relatively weak effects, such as disease factors, genetic factors, and occupational factors. It can be considered that the carcinogenic process of colon cancer is based on the role of dietary factors, combined with the results of multiple links of other factors. With the deepening of etiology and the penetration of multidisciplinary, there is now a new understanding of the carcinogenic mechanism of colon cancer. In the field of epidemiology, modern technology is more widely used, and some factors that are not consistent with previous results are more deeply understood, and the possible causes of epidemiological results will be further clarified. (B) pathogenesis 1. Pathogenesis based on modern biology and epidemiology research, it is increasingly clear that colon cancer is the result of synergy between environment, diet and living habits and genetic factors, the role of carcinogens combined with the cellular genetic background, It leads to the genetic mutation of the cell and gradually develops into cancer. Because of the long course of colon cancer and some obvious stages of precancerous lesions of adenoma, colon cancer has become an ideal model for studying the pathogenesis of tumor and the pathogenesis of malignant tumor. In terms of etiology, in addition to genetic factors, other factors are classified into two categories according to the changes in cytogenetic, namely: genotoxic carcinogens and non-genotoxic carcinogens. Colon cancer is formed by multiple factors and multiple stages, and various molecular events develop. Various factors can be classified into endogenous and exogenous factors, and the occurrence of tumors is the result of internal and external interactions. External factors are nothing more than physical and biological factors, genetic or acquired genetic instability, microsatellite instability and chromosomal instability. In the gradual development and progression of colon cancer, molecular events can be primary genetic events and secondary molecular events. The former is a mutation in the gene structure, and the latter is a change in gene expression during the development and evolution, and does not involve changes in gene structure, such as changes in protein, enzyme levels, and phosphorylation, acetylation or glycosylation in translational modifications. Malignant tumors are increasingly clear in the concept of a class of cytogenetic diseases. In the pathogenesis and pathogenesis of colon cancer, different genetic backgrounds have different susceptibility, which also determines the characteristics of colon cancer pathogenesis. The following three aspects describe the malignant transformation process of colon cancer. (1) Malignant transformation process of colon cancer: the malignant transformation process is the whole process of primary genetic events, and a group of genotoxic carcinogens, ie, carcinogen promoters, initiates multiple attacks on cells, resulting in DNA mutations occur in the corresponding genes, and the genotype changes, leading to genetic transformation of the cells - cancer. In colon cancer, morphologically, its phenotype includes epithelial hyperplasia, adenoma formation, carcinoma in situ, and invasion and metastasis of cancer. Some colon cancers are derived from adenomas. Adenomas may undergo a long period of time from the onset to the formation and associated with atypical hyperplasia, which is beneficial for observation and research. Therefore, more oncogenes and tumor suppressor genes involved in molecular events have been discovered. . The APC gene (adenomatous polyposis coli) and c-myc gene are the primary genetic events involved in the adenoma stage. Cancerous changes occur in adenomas, but also in flat mucosa. Molecular events of hyperplasia of the epithelium include genes related to the adenoma stage, involving a total of at least 9 to 10 gene molecular events, which can be summarized as dominant Oncogenes and recessive anti-cancer genes 2 major categories. 1 dominant proto-oncogene: generally a positive regulator of normal cell growth, a single allele mutation sufficient to cause a change in cell phenotype, ie, genetic structure changes. Even if the gene is mutated only on a single chromosome, its phenotypic change can be caused. Read more...