An epidemiological survey of 145 surveillance sites distributed in 31 provinces/autonomous regions and municipalities directly under the central government in China found that the death rate from pancreatic cancer increased substantially during the 10-year period 1991-2000 (from 1.46 per 100,000 in 1991 to 2.38 per 100,000 in 2000, an increase of 63%). The significant increase in the number of deaths from pancreatic cancer is partly due to the increase in the incidence of pancreatic cancer; it is also partly the result of a clear diagnosis of the underlying cause of death as a result of advances in medical technology and socioeconomic development. Can we find the cause of such a disease that is increasingly dangerous to human health?
The current authoritative view in oncology is that smoking accounts for 30% of the causes of pancreatic cancer, genetic factors for 10%, and dietary factors for 20%. In addition, 40% of the causes are unknown. Therefore, simply quitting smoking and eating a proper diet can reduce pancreatic cancer deaths by nearly half.
So, in what way do these risk factors cause pancreatic cancer?
1.Smoking
Smoking is the most important environmental factor in the development of pancreatic cancer. The compounds in tobacco are transported to the pancreas, where they are biometabolized, opening the magic box for pancreatic cancer to occur. The main components of tobacco that cause pancreatic cancer are: aromatic amines, nitrosamines, nitrites, and nicotine. They attack the genetic material, allowing the expression of some genes (e.g. ras genes) at inappropriate times and locations (i.e. protein synthesis under the direction of these genes). These attacks accumulate over time, and the faulty gene expression gradually pushes the attacked pancreatic cells against human health: the cells become cancerous, invasive and metastatic, leading to human death.
Smokers have about a 3-fold increased risk of pancreatic cancer compared to nonsmokers, which can be reduced to the same level as normal by quitting smoking for 10 years. In lifelong smokers, there is a very clear quantitative relationship between smoking and pancreatic cancer risk in the last 15 years of life – that is, the more you smoke, the greater your risk of pancreatic cancer.
2. Chronic pancreatitis
Chronic pancreatitis is the biggest auto risk factor for pancreatic cancer, more so than smoking. All forms of chronic pancreatitis can lead to pancreatic cancer. Table 1 lists the risk of pancreatic cancer in patients with various forms of chronic pancreatitis. It is important to note that only a small percentage of patients (3-4%) have pancreatitis secondary to pancreatitis.
It is different from the reasoning behind smoking to induce pancreatic cancer. In chronic pancreatitis, under conditions of persistent inflammation, pancreatic cell genetic damage and cell proliferation can occur simultaneously, initiating and promoting the progression of pancreatic cancer. Therefore, the malignant transformation (i.e., carcinogenesis) of chronic pancreatitis is mainly related to the length of onset of pancreatitis. Smoking can accelerate carcinogenesis. Smoking doubles the risk of development and advances the onset of pancreatitis by 20 years in patients with hereditary pancreatitis.
3, diabetes
A relationship between diabetes and pancreatic cancer has been noted for a long time. Diabetes may be a risk factor for pancreatic cancer and may be an early sign of pancreatic cancer. In other words, some patients have diabetes that causes pancreatic cancer, and some patients have pancreatic cancer that causes diabetes. The key is the chronological order of the diagnosis of diabetes and pancreatic cancer. If diabetes is diagnosed first, then it is more likely to belong to the former; if pancreatic cancer is diagnosed first, then the latter is more likely. Of course, such a judgment requires a rigorous premise: the diagnostic methods we have now are sufficient to detect diabetes and pancreatic cancer in any period.
4. Genetic factors
A variety of hereditary tumor syndromes increase the risk of pancreatic cancer. These syndromes include: BRCA2 carriers, familial atypical multiple nevus melanoma syndrome (FAMMM), hereditary pancreatitis, hereditary non-polyposis colorectal cancer (HNPCC), Peutz-Jeghers syndrome, etc. Patients with pancreatic cancer have a 3- to 5-fold increased risk in first-degree relatives (i.e., parents, siblings, children) and an 8-fold increase in smokers in first-degree relatives with pancreatic cancer. Studies of pancreatic cancer family lines have found that the risk of first-degree relatives of pancreatic cancer patients in the family line was 18 times higher than expected.
Another finding of the study of pancreatic cancer family practice is that even with the use of advanced tools like endoscopic ultrasound for screening, the rate of early diagnosis and curative resection of pancreatic cancer remains extremely low. Therefore, no effective method for early diagnosis of pancreatic cancer has been found yet.
5. Dietary and nutritional factors
Diet can promote the occurrence of gastrointestinal tumors, and reasonable nutrition can also prevent tumors. Animal experiments found that not only high fat and high cholesterol diet promotes the occurrence of pancreatic cancer, but also high salt, air-dried, fried, condensed milk and soy foods may increase the risk of pancreatic cancer. Dietary recommendations to reduce gastrointestinal tract tumors include: lowering total dietary calories, reducing fat and preserved food intake, not consuming smoked foods, abstaining from alcohol, and increasing intake of fruits, vegetables and fiber. Foods without hidden storage and additives, natural foods, and microwave-cooked foods may all reduce the risk of pancreatic cancer. Lemon extract, a component of citrus fruits, is a strong inhibitor of K-ras oncoprotein, and the reduction of pancreatic cancer risk by consuming more citrus may be related to lemon extract. The results of studies on coffee and excessive alcohol consumption vary. Limited by the accuracy of dietary information, recall bias, low response rate and other conditions, there is a lack of effective dietary assessment tools today.
6. Occupational factors
The following factors may not cause pancreatic cancer: cyanoethylene, arsenic, asbestos, engine exhaust, electromagnetic fields, formaldehyde, gasoline, dust, cadmium and its compounds, herbicides, iron and its compounds, lead and its compounds, artificial glass fibers, oil mist (gas), wood chips, etc. HCFCs, chromium, nickel, pesticides, PAHs may increase the incidence of pancreatic cancer.
The risk of pancreatic cancer is significantly higher in the metal decontamination and dry cleaning industries, which use HCFC solvents. Organic chlorinated compounds or organic solvents induce pancreatic carcinogenesis by activating K-ras through an indirect pathway.
From the above analysis, we can see that many factors may be associated with the development of pancreatic cancer. Smoking and chronic pancreatitis are the clearest risk factors. Chronic pancreatitis itself is not a key step in carcinogenesis; germ cell mutation, diet, smoking and alcohol abuse accelerate pancreatic cancer development.