What Causes Stomach Cancer?

There are many known risk factors for stomach cancer (also called gastric cancer), but often it's not clear exactly how these factors might affect how cells in the stomach become cancer cells. This is the subject of ongoing research.

Pre-cancerous changes in the stomach

Several changes thought to be pre-cancerous can occur in the inner lining of the stomach.

In atrophic gastritis, the normal gland cells of the stomach are either fewer or absent. There is also some degree of inflammation (in which the stomach cells are damaged by cells of the immune system). Atrophic gastritis is often caused by infection with H pylori bacteria (see below). It can also be caused by an autoimmune reaction, in which a person’s immune system attacks the cells lining the stomach. Some people with this condition go on to develop pernicious anemia or other stomach problems, including cancer.

Another possible pre-cancerous change is intestinal metaplasia. In this condition, the cells that normally line the stomach are replaced by cells that look like the cells that usually line the intestine. People with this condition often have chronic atrophic gastritis as well. This might also be related to H pylori infection.

Both atrophic gastritis and intestinal metaplasia can lead to having too few gland cells, which would normally secrete substances that help protect the cells in the stomach’s inner lining. Damage to the DNA inside these cells can sometimes lead to dysplasia, in which the cells become larger and very abnormal looking (more like cancer cells). In some cases, dysplasia can then progress to stomach cancer.

Changes in genes (DNA) in stomach cancer cells

Recent research has provided clues on how some stomach cancers form. For instance, H pylori bacteria, particularly certain subtypes, can convert substances in some foods into chemicals that cause mutations (changes) in the DNA of the cells in the stomach lining. This may help explain why certain foods such as preserved meats increase a person’s risk for stomach cancer. On the other hand, some of the foods that might lower stomach cancer risk, such as fruits and vegetables, contain antioxidants (like vitamins A and C) that can block substances that damage a cell’s DNA.

Stomach cancers, like other cancers, are caused by changes in the DNA inside cells. DNA is the chemical that carries our genes, which control how our cells function. We look like our parents because they are the source of our DNA. But DNA affects more than how we look.

Some genes control when cells grow, divide into new cells, and die:

• Genes that normally help cells grow, divide, and stay alive can sometimes change to become oncogenes.
• Genes that help keep cell division under control, repair mistakes in DNA, or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that keep oncogenes turned on, or that turn off tumor suppressor genes.

Inherited versus acquired gene mutations

Inherited mutations in some genes (as explained in Stomach Cancer Risk Factors) can increase a person’s stomach cancer risk. But these are thought to cause only a small percentage of stomach cancers.

Most of the gene changes that lead to stomach cancer occur after birth. Some of these acquired mutations might be caused by risk factors such as H pylori infection or tobacco use. But other gene changes may just be random events that sometimes happen inside cells, without having an outside cause.