The etiology of colorectal cancer is not yet fully understood, but it is believed to be primarily related to environmental factors and the result of multiple factors working together.
(1) Environmental factors:
Studies have shown that when residents from low-incidence areas of colorectal cancer in China and Japan migrate to high-incidence areas in Western countries, the incidence of colorectal cancer increases. The increase in incidence is rapid in the first generation and tends to align with the local population in the second generation, indicating a clear upward trend in disease occurrence with changes in the environment. Among various environmental factors, dietary factors are the most important. Countries with high rates of colorectal cancer have diets characterized by high fat, high animal protein, low fiber, and refined grains, known as “Western dietary patterns.” High fat intake in the diet is closely associated with colorectal cancer, especially left-sided colon cancer. Studies by Wynder and others have found that a diet with fat accounting for 40% of total calorie intake in the United States is associated with a higher incidence of colorectal cancer, while the Japanese diet, with fat accounting for only about 12% of total calorie intake and mostly consisting of unsaturated fats, is associated with a lower incidence of colorectal cancer.
Animal experiments have shown that excessive intake of animal fat increases bile secretion, accelerates the accumulation and concentration of cholesterol derivatives in the colon, significantly increases the concentration of neutral cholesterol and bile acids in the colon, and affects the composition of intestinal bacteria. The degradation products of bile acids and neutral cholesterol have carcinogenic and co-carcinogenic effects. A high-fiber diet has the ability to absorb water, which can increase fecal volume and reduce the concentration of carcinogens in the intestine, shorten the residence time of carcinogens in the intestine, and promote the excretion of harmful substances. Surveys have shown that vegetables can significantly reduce the incidence of colorectal cancer, and fruits, vitamin E, and certain minerals also have a certain effect in reducing the incidence of colorectal cancer.
The risk of colorectal cancer in the general population is 1/50. The risk of colorectal cancer in first-degree relatives of colon cancer patients is 1/17, which is three times higher than that of the general population. If two first-degree relatives have colon cancer, the risk increases to 1/6. This familial hereditary factor is more common in colon cancer than in rectal cancer. Approximately 6% to 10% of colorectal cancer cases are related to genetics. The characteristics of hereditary colorectal cancer include a higher occurrence of proximal colon cancer (65%), an earlier onset, and a higher incidence of multicentric tumors. The genetic mechanisms are not well understood at present, but advances in molecular genetics research are expected to elucidate these mechanisms.
(3)Non-cancerous diseases of the colon:
These include ulcerative colitis, polyps, and adenomas. Approximately 3% to 5% of patients with ulcerative colitis develop colon cancer. Among patients with a 20-year history of ulcerative colitis, the incidence of colon cancer is approximately 12.5%. The risk of developing colon cancer in patients with ulcerative colitis is 5 to 11 times higher than that of the general population of the same age group. About 15% to 40% of colon cancers originate from multiple polyps in the colon (polyp disease), and the pre-cancerous stage of these diseases typically takes 5 to 20 years.
Colon adenomas can be classified into three types based on their pathological morphology: tubular adenomas, villous adenomas, and tubulovillous adenomas (mixed type):
- Tubular adenomas account for 80% of colon adenomas. The rate of malignant transformation is approximately 0.7% for adenomas with a diameter <1cm, 4.7% for those with a diameter of 1-2cm, and approximately 10% for those with a diameter >2cm.
- Villous adenomas account for 4% to 5% of colon adenomas, and reported rates of malignant transformation range from 20% to 40%.
- Mixed-type adenomas account for 10% to 15% of colon adenomas, with an average malignant transformation rate of 20%.
In summary, adenomas and adenomatous epithelial hyperplasia are the most important precancerous lesions. In clinical practice, timely removal of adenomas can reduce the incidence of colon cancer. Therefore, it is important to actively treat colon polyps and adenomas in middle-aged individuals to prevent the development of colon cancer in later stages of life. Timely treatment of precancerous lesions is of great significance in preventing colon cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease, with approximately 50% of children of affected individuals developing the condition. Patients with FAP should receive timely and appropriate treatment, as otherwise, 100% of them will develop colon cancer.
Regions in China such as Jiangsu and Zhejiang are endemic areas for schistosomiasis (also known as Japanese blood fluke disease) and are also high-incidence areas for colon cancer. Approximately 10.8% to 14.5% of advanced schistosomiasis cases develop into colon cancer. In 1974, a study in Zhejiang province reported a colon cancer incidence rate of 44.19 per 100,000 population in areas endemic for schistosomiasis, which is comparable to rates in developed Western countries. Research suggests that long-term deposition of schistosome eggs in the colonic mucosa leads to repeated ulceration, repair, chronic inflammation, and adenomatous hyperplasia, eventually progressing to cancer. In Egypt, 12.5% to 17.34% of colon cancer cases are associated with concurrent infection of schistosomiasis caused by Schistosoma mansoni.
Factors that increase the risk of developing colon cancer include a diet low in fresh vegetables, exposure to radioactive substances, and long-term smoking and alcohol consumption. Cruciferous vegetables such as cabbage and rapeseed can protect the intestinal mucosa. Another factor associated with colon cancer is pelvic radiation therapy. Patients, especially women, who have undergone radiation therapy for cervical cancer, for example, may develop colon cancer due to the rectum and sigmoid colon being relatively fixed within the pelvis and continuously exposed to high doses of radiation. Most cases occur 10 to 20 years after radiation therapy, and the incidence of colon cancer is higher among these patients compared to the general population. Some studies have also reported a slightly higher incidence of colon cancer among smokers or alcohol drinkers.