Stomach Cancer Risk in Lynch Syndrome: What You Need to Know

Stomach (or gastric) cancer accounts for approximately 1.5% of all new cancer diagnoses in the United States each year. It is estimated that 1 to 3% of people living with gastric cancer have a hereditary form of the disease that is caused by the inheritance of certain genetic mutations. These mutations can cause familial cancer syndromes that increase your risk of different cancers, one of them being Lynch syndrome.

Lynch syndrome is an inherited genetic disorder that increases your risk of developing various types of cancer. It is well-known for its association with colorectal cancer, as having this condition significantly raises your risk of a colorectal cancer diagnosis by 20% to 80% and at a young age.

However, did you know that Lynch syndrome is also a risk factor for gastric cancer? In Western countries, men and women who have this cancer syndrome carry a lifetime risk of up to 13% when it comes to developing gastric cancer. This is substantially higher than the average American’s risk of less than 1%. Meanwhile, in Eastern Asia where gastric cancer is more common, some studies have found that the cumulative incidence of gastric cancer in Lynch syndrome is as high as 40%. This can be attributed to environmental factors, especially Helicobacter pylori infection rates, that greatly affect gastric cancer risks in people with Lynch syndrome.

There are two types of Lynch syndrome. Type A puts you at a higher risk of colorectal cancer, while Type B increases your chances of having extracolonic cancers, such as ovarian and endometrial cancer.

Lynch syndrome is caused by germline mutations (alterations) in one of five genes: MLH1, MSH2, MSH6, PMS2 and EPCAM. Known collectively as mismatch repair (MMR) genes, they provide instructions for producing their respective proteins. In normal circumstances, MMR proteins act as “spell-checkers” that catch and correct errors in your DNA during cell division. However, when any of the MMR genes are mutated, their protein products lose their spell-checking function. This allows DNA mismatches to accumulate in the affected cells, causing damaged DNA that can subsequently lead to uncontrolled cell growth and eventually cancer. A deficiency in MMR proteins also promotes mutations in other important genes, such as tumor suppressors adenomatous polyposis coli (APC), K-ras and p53.

Lynch syndrome is an autosomal dominant disorder. This means that you only need one mutant copy of the MMR gene to have the condition. So, if one of your biological parents has Lynch syndrome, you have a 50% chance of inheriting the mutated copy of the MMR gene and thereby inheriting the disorder.

Studies have shown that in people with Lynch syndrome, those who carry mutations in the MLH1 and/or MSH2 genes are at a higher risk for gastric cancer than those with mutations in the other MMR genes.

Research has found that among gastric cancer cases in people with Lynch syndrome, intestinal-type gastric adenocarcinomas were predominant. This type of gastric cancer is usually associated with precancerous conditions of the stomach, like atrophic gastritis.

It is estimated that Lynch syndrome occurs in every 1 to 300-500 people, cementing it as one of the most common genetic predisposition syndromes to cancer. So, if you’re worried about your chances of having Lynch syndrome, continue reading here to find out whether you should get genetic testing for the disorder.