Certain factors have been found clinically that may greatly increase the risk of developing the disease. They include.
1. age of onset, most patients develop the disease after the age of 50.
2. Family history: If someone has a first-degree relative, such as a parent, who has had colorectal cancer, his lifetime risk of developing the disease is eight times higher than that of the general population. About a quarter of new cases have a family history of colorectal cancer.
3. History of colon diseases: Certain colon diseases such as Crohn’s disease or ulcerative colitis may increase the chance of colorectal cancer. Their risk of colorectal cancer is 30 times higher than that of normal people.
4, polyps: Most colorectal cancers develop from small precancerous lesions, which are called polyps. Among them, choroidal adenoma-like polyps are more likely to develop into cancer, and the chance of malignancy is about 25%; the malignancy rate of tubular adenoma-like polyps is 1-5%.
5, genetic characteristics: some familial tumor syndromes, such as hereditary non-polyposis colon cancer, can significantly increase the chance of colorectal cancer. And the onset time is much younger.
(I) Causes of incidence
Some epidemiological studies on colon cancer show that: social development, lifestyle and dietary structure are closely related to colon cancer, and there are phenomena suggesting that there may be differences in environmental and genetic factors affecting the development of colon cancer in different sites and age groups. Environment (especially diet), genetics, physical activity, occupation, etc. are possible etiological factors affecting the development of colon cancer.
Dietary factors Epidemiological studies show that 70%-90% of tumor incidence is related to environmental factors and lifestyle, and 40%-60% of these environmental factors are to some extent related to diet and nutrition, so dietary factors are regarded as extremely important factors in tumor incidence.
(1) The mechanism of action of high fat, high protein and low fiber: can be summarized as follows: ① affect intestinal lipid metabolism, high fat diet increases 7a-dehydroxylase activity, leading to increased formation of secondary bile acids, while the role of fiber is the opposite, and through inhibition of reabsorption, dilution and adsorption, chelation, reduce intestinal deoxycholic acid concentration increases solid phase substances in feces and promote excretion; some dietary factors ( such as calcium ions) can reduce the levels of intestinal ionized fatty acids and free bile acids, both of which have damaging effects on the intestinal epithelium; and inhibit the degradation of intestinal cholesterol. Milk, lactose, and galactose have inhibitory effects on cholane redox. ②Fiber also has the effect of changing intestinal flora, affecting the structure and function of intestinal mucosa, and affecting the growth rate of mucosal epithelial cells, mediating intestinal pH, as well as strengthening the mucosal barrier through mucin, reducing the intestinal toxic substances on intestinal epithelium; ③High fat and some carbohydrates can increase the activity of intestinal cell enzymes (such as glucuronidase, ornithine dehydroxylase, nitroreductase, azo oxidase, lipoxygenase, cyclooxygenase) and promote the production of carcinogens and co-carcinogens. (iv) Effect of biomolecular activity. When the cytoplasm is acidified, DNA synthesis is inhibited and the cell cycle is prolonged.
(2) Vitamins: Case-control studies have shown that carotenoids, vitamin B2, vitamin C and vitamin E are all associated with a reduced relative risk of colon cancer development in a dose-response relationship. Vitamin D and calcium have protective effects.
(3) Onion and garlic: The protective effect of onion and garlic foods on the body has been widely appreciated, and the inhibitory effect of such foods on tumor growth has been confirmed in experiments for many times. Garlic oil can significantly reduce the cell damage of colon mucosa caused by dimethylcholanthrene, and can reduce the rate of colon cancer induction in mice by 75%. In a case-control study, the risk of colon cancer in those with high intake of garlic foods was 74% of that in the low intake group.
(4) Salt and cured foods: The relationship between salt intake and cancers of the stomach, colon and rectum was studied in the high salt intake group, and the relative risk of all three cancers increased. The results of the case-control study suggested that the excess risk of colon cancer occurring in those who consumed cured foods more than three times a week was 2.2 times higher than that of those who consumed cured foods less than once (P<0.01), 2.1 times higher for left hemicolectomy and 1.8 times higher for right hemicolectomy. The explanation of this risk factor may be related to carcinogens produced by the food curing process, while high salt intake may be a concomitant state.
(5) Tea: Tea polyphenols are 1 strong antioxidant that can inhibit the carcinogenic effect of carcinogens. Case-control study results, the risk of rectal cancer in those who drink tea (green tea or black tea) more than 3 times a week is 75% of those who drink less than 1 time a week, while it is not closely related to the colon cancer group. In the last 10 years or so, studies have suggested a significant negative correlation between tea consumption and the risk of colon cancer, but the opposite result has also been reported. Because of the paucity of population studies on the protective effects of tea consumption against colon cancer, it is difficult to evaluate the role of tea consumption in the development of colon cancer in humans. The relationship between coffee and colon cancer is difficult to determine.
(6) Trace elements and minerals: ①Selenium: the death rate of many 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 low risk of colon cancer. However, it is thought that these factors may be merely concomitant factors and do not directly affect the risk of colon cancer in the population. ②Calcium: Animal experiments have shown that calcium ameliorates the toxic effects of deoxycholic acid on the intestinal epithelium. It has been suggested that increased concentrations of bile acids and free fatty acids in the intestine can promote the development of colon cancer, while calcium can combine with them to form insoluble saponification compounds, making them less irritating and toxic to the intestinal epithelium. Some epidemiological studies also suggest that calcium intake can play a protective role in preventing the occurrence of colon cancer.
2.Occupational factors and physical activity Insulated asbestos production workers are more common among colon cancer patients, and animal experiments have confirmed that swallowed asbestos fibers can penetrate the intestinal mucosa. In addition, metal industry, cotton or textile industry and leather manufacturing industry, etc. Acrylonitrile, a compound substance frequently applied in the production of plastics, synthetic fibers and rubber, has been shown to induce stomach, central nervous system and breast tumors, and textile workers exposed to this substance have a higher incidence of lung and colon cancer. Nevertheless, colon cancer is not generally considered to be an occupational disease.
In an analysis of occupational physical activity, the risk of colon cancer was found to be 1.4 times higher in those who sit for long periods of time or frequently than in some more physically active occupations, and was more closely associated with cancer of the appendix. The results of case-control study showed that moderate intensity physical activity plays a protective role against colon cancer (especially colon cancer).
Genetic factors It is estimated that genetic factors may play an important role in at least 20% to 30% of colon cancer patients, of which 1% are patients with familial polyposis and 5% are patients with hereditary polyp-free colon cancer syndrome. Eighty to 100% of patients with hereditary familial polyposis may develop malignancy after the age of 59. In addition, left-sided colon cancer occurs in the majority of patients with familial polyposis, while patients with hereditary nonpolyp syndrome tend to develop right-sided colon cancer.
The results of a population-wide case-control genealogical survey (1,328 colon cancer prevalent families and 1,451 population-based control families) showed that the prevalence of colon cancer was significantly higher in first-degree relatives than in second-degree relatives in each prevalent group. The relative risk of colon cancer in first-degree relatives was higher with the younger the age of the pre-decedent, and the relative risk of colon cancer in first-degree relatives was 6 times higher in the ≤40-year-old pre-decedent than in the >55-year-old group. Family members with a family history of colon cancer (first-degree relatives), especially those whose age of colon cancer onset is below 40 years old, should be given great attention.
4.Disease factors
(1) Intestinal inflammation and polyps: chronic inflammation of the intestine and polyps, adenomas and extensive ulcerative colitis for more than 10 years: the risk of colon cancer is several times higher than that of the general population. Patients with ulcerative colitis with severe atypical hyperplasia have about 50% chance of developing colon cancer, and obviously, the risk of colon cancer in patients with ulcerative colitis is higher than in the general population. Our data suggest that the risk of colon cancer is 2.6 times higher in those who have had the disease for more than 5 years than in the general population, while the relationship with rectal cancer is not close. The risk of colon cancer is lower for those with limited and intermittent lesions.
Crohn’s disease is also a chronic inflammatory disease that mostly affects the small intestine and sometimes the colon. There is increasing evidence that Crohn’s disease is associated with the development of adenocarcinoma of the colon and small intestine, but not to the same extent as ulcerative colitis.
(2) Schistosomiasis: The correlation between schistosomiasis endemic areas and the incidence and death rate of colon cancer was explored based on the retrospective survey of tumor deaths in Zhejiang Province from 1974 to 1976 and the Chinese malignancy survey data from 1975 to 1978, as well as the Chinese schistosomiasis atlas. There was a highly significant correlation between the incidence of schistosomiasis and the death rate of colon cancer in 12 provinces and autonomous regions in the south of China and 10 counties in the Jiaxing region of Zhejiang Province. It is suggested that schistosomiasis may be associated with a high incidence of colon cancer in areas where schistosomiasis is severely endemic in China. However, there is little evidence from epidemiological studies on the association of colon cancer with schistosomiasis. For example, at present, in Jiashan County, Zhejiang Province, where schistosomiasis is increasingly controlled, the death rate of colon cancer and the incidence of schistosomiasis in this area were once the highest in China, and the rate of schistosomiasis infection has decreased significantly. However, according to the findings in recent years, epidemiological and pathological studies of colon polyp carcinogenesis have also reported that polyp carcinogenesis is not related to the presence or absence of schistosomal eggs in polyps. In addition, the results of population-based colon cancer screening conducted in the above two regions did not support schistosomiasis as a risk factor for colon cancer. The results of case-control studies did not find a correlation between schistosomiasis history and colon cancer development.
(3) Cholecystectomy: In recent years, there are more than 20 papers on the relationship between cholecystectomy and colon cancer in China. Some of these studies show that the risk of colon cancer, especially proximal colon cancer, can be increased after cholecystectomy. Men have an increased risk of developing colon cancer after cholecystectomy; in contrast, women have a decreased risk of developing rectal cancer after the procedure. It is also believed that the effect of gallbladder removal on colon cancer is greater in women than in men.
It is now generally accepted that the occurrence of tumors is the result of a combination of factors, and colon cancer is no exception. As a disease closely related to the lifestyle of western society, colon cancer is also closely related to its etiology, and the role of dietary factors is considered to be the most important. At present, the etiological model of “high fat, high protein, high calorie and lack of fiber intake” is still dominant, and most of the research results are consistent with this model. Other carcinogenic factors are relatively weak, such as disease factors, genetic factors, occupational factors, etc. It can be concluded that the carcinogenic process of colon cancer is mainly the result of the role of dietary factors, combined with other factors in a multi-linked way. With the deepening of etiological research and multidisciplinary penetration, there is now a new understanding of the carcinogenesis of colon cancer in the etiological hypothesis. As far as the field of epidemiology is concerned, a more extensive application of modern technology and a deeper understanding of some factors with less consistent results in the past will further elucidate the possible etiology suggested by epidemiological results.
(II) Pathogenesis
Based on modern biology and epidemiological research, it is increasingly clear that colon cancer is the result of the synergistic effect of environment, diet and living habits and genetic factors, and the effect of carcinogens combined with cytogenetic background, resulting in the gradual development of cancer due to cytogenetic mutation, because of the long pathogenesis of colon cancer, some of them have obvious pre-cancerous stage of adenoma, so colon cancer has become the most important factor to study the etiology of tumor and the pathogenesis of malignant tumor. The colon cancer has become an ideal model for studying the etiology and pathogenesis of malignant tumors. In terms of etiology, except for genetic factors, other factors are grouped into 2 major categories according to whether they lead to cytogenetic changes or not, namely: genotoxic carcinogens and non-genotoxic carcinogens.
Colon cancer is multifactorial, multi-stage, and formed by the development of various molecular events. Various factors can be categorized as endogenous and exogenous factors, and the occurrence of tumor is the result of interaction between internal and external factors. Exogenous factors include physical, chemical and biological factors, while endogenous factors are genetic or acquired genetic instability, microsatellite instability and chromosomal instability. During the progressive development of colon cancer, molecular events can be primary genetic events and secondary molecular events. The former are mutations in gene structure and the latter are changes in gene expression during developmental evolution, neither of which involve structural changes in genes, such as changes in protein and enzyme levels and their phosphorylation, acetylation or glycosylation in translation modifications. The concept of malignancy as a class of cytogenetic diseases is becoming increasingly clear. In terms of colon cancer pathogenesis and pathogenesis, different genetic backgrounds have different susceptibilities, thus also defining the characteristics of colon cancer pathogenesis, and the malignant transformation process of colon cancer is described from the following 3 aspects respectively.
(1) Malignant transformation process of colon cancer: Malignant transformation process is the whole process of primary genetic events, which is initiated by a group of genotoxic carcinogen, i.e. carcinogen, which strikes the cell several times, resulting in the corresponding genetic mutation of DNA and genotype change, leading to the genetic transformation of the cell – cancer. genetic transformation – carcinogenesis. In colon carcinogenesis, morphologically, the phenotype includes stages of epithelial hyperplasia, adenoma formation, carcinoma in situ, and infiltration and metastasis of carcinoma.
APC genes (adenomatous polyposis coli) and c-myc genes are the first primary genetic events involved in the adenoma stage.
The molecular events of epithelial hyperplasia include genes related to the adenomatous stage and involve at least 9-10 genes in total, which can be categorized into 2 major groups: dominant-acting proto-oncogenes and recessive-acting oncogenes.
(1) Dominant-acting proto-oncogenes: they are generally positive regulators of normal cell growth, and mutations in a single allele are sufficient to change the cell phenotype, i.e., alter the gene structure. Even mutations in only a single chromosome can cause phenotypic changes.
A. c-myc gene: It is a pre-adenoma mutated gene, located in the 8q24 region. c-myc is overexpressed in about 70% of colon cancers, especially in left-sided colon cancers, up to several-fold to tens of-fold. The APC gene is intrinsically linked to the overexpression of c-myc, and none of those without c-myc mutation have lost APC gene. c-myc gene also has the function of regulating ras gene.
B. Ras gene: Colorectal adenomas greater than 1 cm have a 50% chance of detecting point mutations in at least one of the Ras gene family (H-ras, K-ras and N-ras), and about 10% in those <1 cm. The mutation rate is directly related to the degree of atypical hyperplasia of adenomas, and can be used as a signal of adenoma with malignant potential. The mutation rate has been used to estimate the degree of malignancy and to predict prognosis. The majority of ras mutations occur in codons 12 and 13 of the Ki-ras gene, accounting for 88% of all mutated codons, with codon 61 being the other common site. In the Chinese colon cancer study, two cell lines, HR8348 and Hce8693, both had Ki-ras codon 12 with a G→C base transition at its second site. In 35 Chinese colon cancer cells, 37% had Ki-rar gene fragments, and in China, mutated Ki-ras gene fragments were successfully detected in the stool of 33.3% (6/18) of colon cancer patients by non-radionuclide methods, providing a possibility for molecular diagnosis.
The recessive oncogene: It is a negative regulator. When a single allele is missing or mutated, the corresponding gene on the other chromosome can still maintain its original function and normal phenotype, but only when both alleles are missing or mutated, it will lead to functional disorder and phenotypic change of the gene, resulting in uncontrolled cell proliferation and then cancer.
A. APC gene: APC gene was first found and cloned in familial adenomatous polyposis (FAP), located at 5q21. FAP is an autosomal dominant syndrome, FAP can also be associated with extracolonic lesions, such as Gardner syndrome with bone disease or fibrosis, Turcot syndrome with brain tumor, all have genetic deletion of chromosome 5q21 and loss of alleles ( loss of heterozygosity). In colon cancer without family history, 35-60% of patients also have this gene loss.
B. Mutations in the MCC (mutated in colorectal cancer) gene: The MCC gene is also located at 5q2l, which is close to the APC gene locus, and the two have similar sequences of fragments in structure. However, mutations in the MCC gene are rare in the FAP family, and about 15% of sporadic colon cancers are inactivated by somatic mutations, which occur in the G-C base pair (G-C→A-T).
C, DCC (deleted in colorectal cancer) gene deletion or mutation: about 50% of late stage adenomas and more than 70% of colon cancers can be detected with heterozygous loss in chromosome 18q21 region. What is the risk of heterozygosity?” href=”http://jbk.heyi365.com/keshi/pifu/pifubing/490b3.html” target=”_blank”