How is rectal cancer caused?

Risk factors leading to colorectal cancer can be divided into two categories: relative risk and absolute risk.

1. Dietary factors

(1) Fat, cellulose and calories: Dietary factors play an extremely important role in the occurrence of colorectal cancer. At present, colorectal cancer ranks second in the world, second in western developed countries and eighth in some underdeveloped countries. Epidemiological observation and experimental research show that diet plays a decisive role in the occurrence of colorectal cancer, and the increase of fat consumption is parallel to the increase of incidence of colorectal cancer. The direct measurement of dietary fat content shows that people who eat a lot of fat have a high mortality rate of colorectal cancer. The study of immigrants from low-fat diet to high-fat diet found that the incidence of colorectal cancer was significantly higher than that in the original place. The mortality rate of colon cancer has increased significantly among immigrants from Japan to Hawaii, and immigrants from Poland to Australia have also shown this increase. Many case-control studies support the correlation between fat intake and colorectal cancer. However, other epidemiological data have not confirmed this correlation, especially in different parts of the same country, such as Utah. The incidence of colon cancer in the United States is far lower than the average incidence in the United States, and the fat consumption of each population is the same. The reason for this contradiction in epidemiological data is that the protective dietary factors for colon cancer are not considered. A study in northern Europe found that the incidence of colon cancer in Danes was significantly higher than that in Finland. Although the fat intake is the same, Finns consume more cellulose than Danes, which indicates that cellulose may have the carcinogenic effect of regulating fat. Recently, Willett and others once again confirmed that the occurrence of colon cancer is positively related to the consumption of animal fat. In addition, a recent epidemiological study analyzed the relationship between fat intake and various cancers, and found that fat intake was positively correlated with the occurrence of six cancers, including colorectal cancer.

Most epidemiological data show that colon cancer is related to total fat intake, not to special food fat. But there are also epidemiological studies to explain the relationship between fat types and colon cancer; Some studies believe that it is related to animal fat, while others support that plant fat has the greatest effect. In the experimental colon cancer induced by dimethylhydrazine (DMH), the animal with high concentration of vegetable oil and polyunsaturated fat has a higher incidence. On the contrary, highly polyunsaturated fish oil and monounsaturated olive oil have no enhancement effect on chemically induced animal colon cancer. Reddy et al. (199 1) reported that in a group of experiments of chemically induced colon cancer, it was found that fat type, fat consumption and time of fat consumption all had effects on the occurrence of colon cancer. There are two reports that monounsaturated fat has a protective effect on colon cancer. Anti et al. (1992) reported a double-blind controlled study, in which a patient with colon adenoma underwent biopsy after fish oil 12 weeks. The proliferation rate of the upper colon crypt slowed down within 2 weeks after fish oil supplementation. This deceleration is thought to inhibit the formation of adenoma.

The biochemical mechanism of dietary fat promoting colon cancer has not been confirmed, and it is speculated that there are several mechanisms: ① dietary fat causes the increase of steroid hormones in bile, which is harmful to colon epithelium and can cause excessive proliferation of colon epithelium; ② Free radicals produced in the process of lipid peroxidation can promote canceration; ③ Some fatty acids can promote their carcinogenicity by binding with the cell membrane, causing changes in the fluidity of the cell membrane and reacting with carcinogens; ④ Excessive linoleic acid can increase the synthesis of some prostaglandins, while the latter can promote cancer and stimulate cell proliferation; ⑤ Food fat determines the properties of intestinal bacteria and plays an important role in the metabolism of carcinogens; The carcinogenic effect of fat lies not in its special chemical composition, but in its heat density. Because fat has the highest calorie density, it is the most carcinogenic.

At present, it is not known to what extent food fat should be limited to reduce its carcinogenic effect on colon. In the United States and some western European countries, the average fat content accounts for about 40% of the total calories, which is in sharp contrast with the diet in third world countries, where fat only accounts for 10% ~ 25% of the total calories. Animal studies show that when the dietary fat increases from 10% to 40% of the total calories, there is a dose to induce colon tumors.

Another factor related to colorectal cancer in the diet is cellulose. Burkitt and Trowell first proposed that the diet of African blacks contains more cellulose, so the mortality rate of colorectal cancer is lower than that of whites, who consume little cellulose. However, the results of subsequent epidemiological studies are inconsistent. This inconsistency may be due to the fact that dietary fibres is not a special chemical entity, but a variety of compounds. The only similarity is that it comes from plants and is resistant to the action of human digestive enzymes. Different cellulose has different physiological and chemical characteristics, which can affect colon environment and colon mucosa in many ways. Some dietary fibers, such as bran, pass through the colon unchanged. Other cellulose gums are almost completely crushed by bacteria in colon, and most of them become short-chain fatty acids. These fatty acids regulate the pH value of colon and are used as the main energy source by colon cells.

Most epidemiological studies only analyzed the relationship between foods containing cellulose and colon cancer as a whole, but did not study special cellulose. However, in some studies, the risk of colorectal cancer is related to special fiber or foods containing special fiber. Kunes and others found that cruciferous vegetables such as broccoli, cabbage and soup have protective resistance to colon cancer. However, it is impossible to know whether its protective effect is due to cellulose in these vegetables or chemical preventive substances such as sulforaphane, which can stimulate enzymes to neutralize free radicals. Animal models show that special food cellulose bran and plant cellulose have protective effects on colon cancer caused by carcinogens, while pectin does not. However, some cellulose can cause changes in the colonic mucosa, which indicates that it can promote the canceration process. In experimental colon cancer, eating wheat bran and pectin can increase DNA synthesis, mucosal quality and cell migration, but oat bran can not change these changes. It must be emphasized that these influences may be inconsistent and may be related to race, gender or other factors. Considering that dietary fibres is composed of different physiological and chemical components, if it does have a protective effect, it seems that it may be unique to some celluloses.

The mechanism of cellulose in preventing colon cancer is not clear, but there are several possibilities: ① shortening the transmission time in colon, thus shortening the contact time between carcinogens in intestinal cavity and colon mucosa; ② Cellulose is combined with carcinogen in intestinal cavity and diluted, thus neutralizing its harmful effects; ③ Changes of colonic bacteria metabolizing bile acids; ④ After dietary fibres was metabolized into short-chain fatty acids in colon, the pH value in colon decreased. The decrease of pH value leads to ionization of free fatty acids and bile acids, which may be harmful. Recently, Cummings reported that the incidence of colon cancer in 20 people in 12 countries was negatively correlated with the amount of feces, and pointed out that when the intake of cellulose was >: 18g/d, the amount of feces was >: 150g/d, the occurrence of colon cancer could be prevented.

Animal studies and some epidemiological data show that excessive calorie intake and obesity will increase the incidence of various organ cancers. Tanaenbaum's early and recent studies have proved that limiting calorie intake and losing weight can inhibit chemically induced tumors, including colon cancer. International epidemiological studies and case-control studies show that increasing calorie consumption and weight gain will increase the risk of colon cancer. A study by the American Cancer Society found that the body mass index is positively correlated with the incidence of colon cancer. This phenomenon is also found among Japanese living in Hawaii. However, some epidemiological studies have not found the relationship between weight and colon cancer. At the recent seminar on "calorie and energy consumption in cancer occurrence", the conclusion was that "overnutrition is directly related to the high risk of cancer". However, it must be noted that there are complex relationships among calorie intake, energy consumption, weight and endocrine environment. Even if calorie intake does increase the occurrence of cancer, it is still necessary to judge whether the main factors are calorie intake, metabolic rate, direct effect of body weight or comprehensive effect.

According to the above situation, in recent years, the United States and other countries have recommended some dietary requirements to prevent cancer. The American Cancer Society (ACS) and the National Cancer Institute (NCI) recommend the following programs: ① Reduce fat intake to less than 30% of total calories. ② Increase the intake of cellulose to 20 ~ 30g/d, with a maximum of 35g/d ... ③ Including all kinds of fruits and vegetables. 4 prevent obesity. ⑤ moderate drinking. ⑥ Try to eat less salted and smoked food.

Reducing fat to 30% of total calories in NCI diet may be too little, but reducing fat to 20% ~ 25% of total calories may be more appropriate.

(2) Vitamins and minerals: The incidence of colon cancer is influenced by the environment. Among environmental factors, epidemiological research focuses on eating habits and food choices. In addition to fat, cellulose and calories, micronutrients and minerals with antioxidant effects were also studied. Antioxidants can scavenge or neutralize some oxygen metabolites, which are called oxygen free radicals and singlet oxygen. These metabolites are formed in the routine biochemical process of the whole body, and they may be dangerous because they can damage DNA, lipid membrane and protein. This kind of molecular damage to cells, if not suppressed, will promote the formation of cancer. Several vitamins, minerals and trace elements have antioxidant effects. Therefore, scholars focus on observing whether colon cancer increases when micronutrients and VitA, c and e values are low.

2. Genetic factors are important factors for adenomatous polyposis and colorectal cancer. There are two kinds of patients with outstanding clinical manifestations, one is familial adenomatous polyposis (FAP), the other is hereditary nonpolyposis colorectal cancer (HNPCC), and it also includes site-specific colorectal cancer and cancer family syndrome. Except for these two types of patients, they are all called sporadic cases.

FAP is an autosomal dominant genetic disease with an penetrance of 95%, and the incidence of its children is 50%. If this disease is not treated, it will eventually become cancerous. The mutation of APC gene can be detected in 40% ~ 70% of patients, but it only accounts for about 1% in colorectal cancer.

HNPCC was originally called Cancer Family Syndrome (CFS), and recently it was called Lynch Syndrome Type I and Type II. The main feature of Lynch syndrome is that there are no multiple colonic polyps. But the gene transfer mode of Lynch syndrome is autosomal dominant inheritance. It accounts for about 6% of the total number of colorectal cancer. Unlike FAP, it has no premonitory phenotypic signs or biomarkers to help clinicians identify cases or families. Therefore, the only key to diagnose Lynch syndrome is family history. Lynch syndrome type I is characterized by site-specific colorectal cancer, which occurs at an early age, mostly in the right colon (up to 70%), and there are more simultaneous or metachronous multiple primary colon cancers. Lynch syndrome type ⅱ, that is, in addition to Lynch type ⅰ characteristics, endometrial cancer and ovarian cancer are common. In some Lynchⅱⅱ families, there are other malignant tumors such as ureteropelvic transitional cell carcinoma, gastric cancer, small intestine cancer, pancreatic cancer and so on.

As for the so-called sporadic colorectal cancer, it is now found that its familial risk increases. The risk of the first generation relatives of patients with colon cancer is increased by 2-3 times, and the relatives of patients with colorectal adenoma are also at risk of colorectal cancer. Colonoscopy data show that the first generation relatives of colon cancer patients are twice as likely to suffer from adenomatous polyp. If the age of colon cancer patients at diagnosis is

Studies on these relatives show that the increase in family risk is due to mild to moderate genetic susceptibility. This susceptibility exists in most patients with colorectal cancer and adenomatous polyp. Existing data show that genetic factors determine individual susceptibility to colorectal cancer, while environmental factors regulate this susceptibility.

3. Colitis diseases Among colitis diseases, three diseases are most closely related to colorectal cancer. Chronic ulcerative colitis is recognized as a disease with high canceration risk, but its canceration risk is related to the length of the course, the location and scope of the lesion. When the disease stage reaches 10 years, the risk begins to increase. If the lesion is confined to the left colon, the risk increases, and the risk of cancer in patients with ulcerative proctitis and ulcerative colitis increases. Therefore, on the whole, the risk of colorectal cancer in patients with ulcerative colitis is 10 ~ 25 times that in patients without colitis, but a large group recently reported that the cumulative risk in 25 years is only 9%. However, only 1% of colorectal cancer patients have ulcerative colitis. The incidence of ulcerative colitis is relatively high in North America and Western Europe, and relatively rare in China, so it is even rarer in colorectal cancer.

Schistosomal colitis is also a disease with high canceration rate, which is very prominent in schistosomiasis endemic areas in China. For example, Jiashan and Haining in Zhejiang are both endemic areas of trematode and high incidence areas of colorectal cancer, and their morbidity and mortality are the highest in rural areas of China, accounting for 1/4 of malignant tumor deaths, which is 4 ~ 9 times higher than other provinces and cities. According to various reported clinical data, Zhou Xigeng and others reported that there were 266 cases of schistosomiasis in 1754 cases of colorectal cancer, accounting for 15. 17%. The Cancer Hospital affiliated to Shanghai Medical University reported 1 120 cases with schistosomiasis, accounting for 18. 1%. Hangzhou Cancer Hospital reported that among 507 cases of colorectal cancer, 27.4% were accompanied by schistosomiasis. Among the 3 14 cases of colorectal cancer reported by the First Hospital of Jiaxing, Zhejiang, 96. 1% were accompanied by schistosomiasis. These data fully reflect the close relationship between colorectal schistosomiasis and cancer. Due to the long-term deposition of Schistosoma eggs in colorectal mucosa, chronic inflammation, repeated ulcer formation and repair. It leads to the formation of mucosal granulation tissue and then canceration. Among 3678 patients with advanced schistosomiasis in the First Hospital of Jiaxing City, Zhejiang Province, 24 1 patient (6.55%) was accompanied by granuloma of colorectal schistosomiasis, of which 62.7% was accompanied by adenocarcinoma, which strongly indicated that schistosomiasis was an important factor in the occurrence of colorectal cancer.

4. Colorectal adenoma Colorectal adenoma is the most common polypoid lesion in clinic, and about 2/3 of colorectal polyps are adenomas. Histologically, adenomas are divided into three types: tubular, villous and tubular villous, among which tubular adenomas are the most common, and pure villous adenomas are rare, accounting for only 5% of all adenomas. This classification of adenoma is mainly based on the proportion of villi components, because the epithelial structure of adenoma is uneven in morphology. When the villous component accounts for 0% ~ 25%, it is called tubular adenoma, 25% ~ 75% is tubular villous adenoma, and 75% ~ 100% is called villous adenoma. From the naked eye, adenoma can be divided into three types: pedicled type, broad base type and flat type. Not all adenomas are polypoid, but only a slight lump on the mucosal surface, which is called flat polyp. Larger adenomas and villous adenomas are more prone to high variation.

5. Personal high-risk factors Patients who have suffered from colorectal cancer in the past have a significantly higher risk of colorectal cancer than normal people. According to the data of StMarks Hospital, among the 33,865,438+0 patients who underwent colorectal cancer resection, the incidence of metachronous colorectal cancer was 65,438+0.5%, and in the cases followed up for 25 years, the incidence was 5%: if the adenoma was removed at the same time during resection, the incidence was 65,438. Although most metachronous colorectal cancer occurred within 10 years after resection, it was reported that the incidence of metachronous colorectal cancer was 3.4%, and 67% occurred above 1 1 year after the first resection. It shows that the risk of metachronous colorectal cancer seems to be lifelong.