Stomach cancer, also known as gastric cancer, originates when cells in the stomach lining grow out of control, forming a tumor. While hereditary factors increase risk for some people, the majority of diagnoses are not directly linked to a gene mutation inherited from a parent. A small but significant number of cases do have a clear inherited genetic basis. Understanding the difference between cancer that develops randomly and cancer tied to a family history is important for risk assessment and prevention.
Understanding Sporadic and Inherited Gastric Cancer Risk
The vast majority of stomach cancer cases, estimated at 90% to 95%, are classified as sporadic. Sporadic cancer occurs as an isolated event in an individual who does not have an identifiable inherited genetic predisposition. These cases arise from random DNA damage and accumulated mutations that occur in a single cell over a person’s lifetime, typically due to environmental exposures or aging.
In contrast, hereditary stomach cancer accounts for about 1% to 10% of all diagnoses. This type is defined by a strong family history and is often caused by a specific germline gene mutation passed from parent to child. Individuals who inherit these mutations are born with a significantly elevated lifetime risk of developing the disease compared to the general population. This distinction is fundamental to determining appropriate screening and prevention strategies.
Specific Genetic Syndromes Linked to Stomach Cancer
The most well-known inherited condition that increases stomach cancer risk is Hereditary Diffuse Gastric Cancer (HDGC). This syndrome is associated with a mutation in the CDH1 gene, which produces the E-cadherin protein. A mutation disrupts E-cadherin’s function of helping cells stick together, leading to the aggressive, poorly cohesive diffuse type of stomach cancer.
Individuals inheriting a pathogenic CDH1 variant face a highly elevated lifetime risk of developing diffuse gastric cancer (up to 70% for men and 56% for women by age 80). Female carriers also have an increased risk of developing lobular breast cancer. Due to the high risk and difficulty in early detection, prophylactic total gastrectomy—the surgical removal of the stomach—is often recommended for confirmed CDH1 carriers.
Other hereditary syndromes also increase the risk for stomach cancer, though usually to a lesser degree than HDGC. These include:
- Lynch Syndrome, which primarily raises the risk for colorectal and endometrial cancers, but also increases the risk of intestinal-type stomach cancer.
- Familial Adenomatous Polyposis (FAP), which is characterized by numerous polyps in the colon and increases the chance of developing stomach tumors.
- Rare syndromes, such as Peutz-Jeghers Syndrome and Juvenile Polyposis Syndrome.
Non-Genetic Causes and Environmental Triggers
Since the majority of gastric cancers are sporadic, environmental and lifestyle factors are the primary drivers of the disease worldwide. The most significant non-genetic risk factor is chronic infection with the bacterium Helicobacter pylori (H. pylori). This infection causes long-term inflammation of the stomach lining, which can lead to precancerous changes over many years.
Dietary habits also play a substantial role. High consumption of foods preserved by salting, smoking, or pickling, such as cured meats, increases the risk. These foods often contain nitrates and nitrites that can convert to carcinogenic compounds in the stomach. Conversely, a diet rich in fresh fruits and vegetables appears to offer a protective effect.
General lifestyle choices, including tobacco use and heavy alcohol consumption, further increase the likelihood of a diagnosis. Smoking approximately doubles the risk of stomach cancer, especially for tumors near the esophagus. These environmental factors contribute to the random DNA damage that characterizes sporadic cancer development.
When to Seek Genetic Testing and Screening
Individuals should consider seeking genetic counseling and testing if their personal or family history meets criteria suggesting a hereditary syndrome. Testing for the CDH1 gene is recommended if there are two or more cases of diffuse gastric cancer in close relatives, or if one relative was diagnosed before age 50. The presence of both diffuse gastric cancer and lobular breast cancer in a family is another strong indicator for genetic evaluation.
Genetic counseling involves reviewing a detailed family history and explaining the medical, psychological, and ethical implications of testing. If a pathogenic germline mutation is identified, the management plan shifts to intensive surveillance or prophylactic measures.
Carriers of certain mutations, like those for Lynch syndrome, are often advised to undergo regular upper endoscopy (gastroscopy) starting in their 30s to look for early signs of cancer. For those with the high-risk CDH1 mutation, preemptive removal of the stomach is a major consideration to eliminate the high lifetime risk. Management for all hereditary risks includes testing for and treating any co-existing H. pylori infection.