What is stomach cancer? First of all, let’s introduce the stomach to you. The stomach is an important organ for storing and digesting food. It is located in the middle of the esophagus and the small intestine, and is divided into the esophagogastric junction, the fundus, the body, the sinus and the pylorus from top to bottom. The stomach wall is composed of different layers, the innermost layer is the mucosal layer, which is the main structure constituting the gland, and outwardly the submucosal layer, the muscular layer and the plasma layer in that order. Gastric cancer is a type of tumor that originates from the stomach wall, while the majority of gastric cancers originate from the glands and are therefore called adenocarcinomas. The gastric cancer we present here refers to gastric adenocarcinoma only, excluding other types of gastric cancer such as gastric lymphoma, gastric mesenchymal tumor and neuroendocrine tumor. These tumors are distinctly different from the common gastric cancer because of their different origins and are not discussed here. Is the incidence of gastric cancer high? Worldwide, gastric cancer is most common in East Asia, South America and Eastern Europe, with nearly half of the patients coming from China. 989,000 new cases of gastric cancer were diagnosed worldwide in 2008, with China accounting for 46.8% of the total. In China, compared with other malignant tumors, stomach cancer has the second highest incidence rate and the third highest mortality rate, which shows that stomach cancer is a disease that deserves our attention. The incidence of gastric cancer is on the rise with age, and about two-thirds of gastric cancer patients are over 65 years old, and most of them are men, and men are about twice as likely to suffer from gastric cancer as women. What are the causes of gastric cancer? People call tumor a malignant disease because we neither know how it occurs nor is it difficult to cure it. Although there are countless scholars all over the world and various researches have been conducted on tumors, we still do not know the exact cause of tumor occurrence. However, research findings have at least told us which risk factors may increase the risk of developing stomach cancer. Knowing these factors can help us a lot in preventing the occurrence of stomach cancer. What are the risk factors for gastric cancer? First of all, it should be noted that risk factors are not the cause of stomach cancer, but just may increase the risk of developing the disease and need to be brought to your attention. In the following, we will introduce risk factors of gastric cancer from several aspects, such as infectious factors, lifestyle, genetic background, immune factors, benign diseases that may be related to gastric cancer, pre-cancerous lesions of gastric cancer, and the influence of surgery. Infectious factors: H. pylori infection is the most clear and important risk factor for gastric cancer. It is a spiral-shaped bacterium, much like an “S” or arc, with two to six flagella at one end of the bacterium. Above the gastric mucosal cells, there are at least three other protective layers: a mobile mucus layer, a fixed mucus layer, and a tight, intact cellular arrangement. Helicobacter can burrow through the two layers of mucus and then suck tightly on top of the mucosal layer of cells and secrete glue-like adhesions that stick the bacteria to the epithelium; the flagella can also insert between the cells and hook them tightly; the hairs on the bacteria can twist together with the cell surface again, like a knotted rope tangled together, so that the bacteria are difficult to be removed. H. pylori has a very destructive effect on the cells, it has a variety of “weapons”, for example, it can secrete a large number of urease, this enzyme can break down the blood, body fluids in the urea, releasing ammonia gas. Ammonia is a toxic alkaline gas that poisons mucosal epithelial cells, and the higher the concentration of ammonia, the greater the inflammation in the stomach, and it also surrounds Helicobacter like a cloud, helping the bacteria to resist corrosion by stomach acid. In addition, Helicobacter can also secrete a variety of other cytotoxins that destroy the mucus and cells that protect the gastric mucosa, and after opening the gap, the gastric acid and pepsin in the stomach lumen follow to take advantage of the situation and destroy the gastric mucosal cells, producing various manifestations of inflammation. Two doctors from Australia, Marshall and Warren, discovered that this bacteria is associated with chronic gastritis and peptic ulcers, and won the Nobel Prize in Medicine in 2005 for this. Subsequent studies found that Helicobacter is not only associated with inflammation, but also closely related to the production of gastric cancer and gastric lymphoma. Long-term chronic inflammation and various toxic factors can stimulate some very dangerous changes in the epithelial cells of the gastric mucosa, which can lead to gastric cancer. When H. pylori is completely eradicated, pre-cancerous lesions of the stomach such as atrophic gastritis, intestinal chemosis, and heterogeneous hyperplasia are significantly relieved. About 50% of people worldwide will be infected with H. pylori, and it is important to treat this infection as the bacteria can be easily spread through saliva or feces under poor economic conditions and living environment. Nowadays we have been able to cure this infection by applying triple therapy or diphtherapy containing antibiotics. Another infection that may be associated with gastric cancer is viral infection. EBV is detected in about 5-10% of gastric cancer cells. The mechanism by which this viral infection causes gastric cancer is not clear, except that it has been found clinically. This type of gastric cancer is usually slower to grow and slower to metastasize and spread. Lifestyle: The most important factor that has an impact on stomach cancer in daily life is diet. Before man invented the refrigerator, it was very difficult to keep food fresh. Therefore, people cured food by salting, smoking or other fermentation methods so that it can be preserved for a long time, but frequent consumption of such food can cause great damage to the stomach. Too much salt can make H. pylori more easily infected and invasive, and salt can also damage the mucous membrane layer of the stomach and directly lead to the occurrence of stomach cancer. Smoked or cured foods contain a large amount of nitrate, nitrite or polycyclic aromatic hydrocarbons, which will be transformed into various cancer-promoting substances by the action of bacteria in the stomach. Therefore, large and regular consumption of salted, smoked or other cured foods can increase the risk of stomach cancer. Smoking is also an important risk factor for cancer. It is widely accepted that smoking is associated with lung and oral cancers. In fact, most people do not know that smoking also increases the risk of stomach and esophageal cancer. Nicotine and other harmful substances in cigarettes not only enter the body through the respiratory tract, but also cause damage to the mucous membrane of the digestive tract through their effects on blood vessels and epithelial cells. The incidence of gastric cancer, especially in the part of the stomach near the esophagus, is doubled in people who smoke, so it is important to avoid smoking as much as possible. Genetic background: There are several genetic factors that may increase the risk of gastric cancer. There is a rare heritable mutation in a gene called epithelial calmodulin (E-cadherin, CDH1), and about 70% to 80% of people with this mutation will eventually develop gastric cancer. Gastric cancer caused by this genetic mutation is called hereditary diffuse gastric cancer and has a very poor prognosis. Women with this mutation may also develop a form of breast cancer. Testing for this genetic mutation is already available at some oncology centers. People with the mutation may need regular checkups to monitor for the development of gastric cancer and to discuss the need for prophylactic gastrectomy surgery if necessary. Some inherited mutations may predispose to cancer in other parts of the body, while also putting people at a slightly increased risk of stomach cancer. For example, hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome). This is an inherited genetic defect disease caused mostly by defects in the MLH1 or MSH2 genes, but may also be caused by defects in other genes, including MLH3, MSH6, TGBR2, PMS1 and PMS2. These genetic defects are what we commonly refer to as microsatellite instability. People with this genetic defect develop multiple colonic adenomas, which are more likely to develop into cancer than normal adenomas. The risk of colorectal cancer in this group begins to increase from the age of 20, and by the age of 60 57% to 80% will have developed colorectal cancer. The incidence of gastric cancer also increases in these patients. Familial adenomatous polyposis (FAP) is an inherited disease caused by a mutation in the APC gene. Patients develop multiple polyps in the colon, stomach, and small intestine, and their risk of colorectal cancer is significantly increased, as well as a mildly increased risk of gastric cancer. Inherited mutations in the BRCA1 and BRCA2 genes are high risk factors for breast and ovarian cancer, and the incidence of gastric cancer is also higher in such patients. These genetic defects can be detected early through genetic screening and genetic counseling. In some advanced oncology centers in China, such genetic screening is already available. These patients with genetic problems need to undergo regular colonoscopy and gastroscopy to facilitate early detection of the disease. In addition, having a family history of gastric cancer in first-degree relatives (parents, siblings or children) also increases an individual’s risk of developing gastric cancer. This may also be related to the genetic mutations mentioned earlier, except that there are many such mutations that have not yet been discovered by scientists. In such cases, regular checkups are also needed for early detection of the disease. Immune factors: When the body’s immune system is too weak or too strong, it can cause disease, and cancer is often associated with a weak immune system. There is a disease called “common variable immunodeficiency (CVID)”, which increases the risk of stomach cancer in patients whose immune system is unable to produce enough antibodies against germs, causing frequent infections and other problems such as atrophic gastritis and pernicious anemia, which may eventually lead to stomach cancer and stomach lymphoma.