Stomach cancer, also known as gastric cancer, is a global health concern. While most cases are not inherited, some are linked to genetic factors passed down through families. Understanding genetics can help individuals assess their risk and explore preventive strategies, especially for those with a family history of stomach cancer.
The Role of Genetics in Stomach Cancer
Genetics influences stomach cancer development through inherited gene mutations that increase susceptibility. These mutations are present from birth and can be passed from parent to child. Specific hereditary syndromes are associated with an elevated risk, often involving genes that play roles in cell growth, repair, or adhesion.
One prominent condition is Hereditary Diffuse Gastric Cancer (HDGC), primarily linked to mutations in the CDH1 gene. This gene produces E-cadherin, a protein important for cell adhesion. When CDH1 is mutated, cells may lose normal adhesion, increasing the likelihood of diffuse-type stomach cancer. Individuals with CDH1 mutations face a high lifetime risk, estimated between 37% and 87% by age 80.
Lynch Syndrome is another inherited condition that increases stomach cancer risk. It results from mutations in DNA mismatch repair genes, including MLH1, MSH2, MSH6, and PMS2. While primarily associated with colorectal and endometrial cancers, Lynch Syndrome can raise the lifetime risk of stomach cancer to up to 13%.
Other genetic syndromes also contribute to stomach cancer predisposition. Familial Adenomatous Polyposis (FAP), caused by APC gene mutations, leads to numerous polyps in the colon and increases stomach cancer risk. Peutz-Jeghers Syndrome (PJS), linked to STK11 gene mutations, is characterized by polyps throughout the digestive tract and elevates the risk of various cancers, including stomach cancer.
Identifying Hereditary Risk
Recognizing individuals and families at hereditary risk relies on a thorough evaluation of family medical history. Patterns like multiple family members diagnosed with stomach cancer, especially diffuse type, or early cancer onset can indicate an inherited predisposition. The presence of other cancer types in the family, such as lobular breast cancer alongside diffuse stomach cancer, can also be a significant indicator.
Genetic counseling plays a central role in this identification process. A genetic counselor reviews personal and family medical histories to assess the likelihood of an inherited cancer syndrome. They discuss genetic testing implications, including benefits and limitations, helping individuals make informed decisions. This consultation provides a comprehensive understanding of risk factors and inheritance patterns.
Genetic testing is recommended for individuals meeting specific criteria, such as a strong family history of diffuse gastric cancer or a personal diagnosis at a young age. Testing involves a blood or saliva sample, analyzed for mutations in genes like CDH1 or Lynch Syndrome genes. A positive result confirms an inherited mutation, while a negative result can help rule out certain hereditary conditions.
Managing Hereditary Stomach Cancer Risk
Individuals with hereditary risk, particularly those with CDH1 gene mutations, have specific management strategies. Regular surveillance protocols involve frequent endoscopic screenings of the stomach. For HDGC, this means annual upper endoscopy with multiple biopsies to detect early signs of diffuse gastric cancer, which is difficult to identify due to its infiltrative nature.
Prophylactic gastrectomy, stomach removal surgery, is a consideration for CDH1 mutation carriers due to the high lifetime risk of diffuse stomach cancer. This procedure significantly reduces cancer development risk, with many choosing to undergo it in early adulthood. While it has nutritional implications, such as the need for lifelong vitamin B12 supplementation, individuals generally adapt to a modified diet and lead normal lives.
For those with other hereditary syndromes like Lynch Syndrome or FAP, surveillance protocols include regular upper endoscopies, with frequency depending on the specific syndrome and individual risk. Lifestyle modifications, such as avoiding smoking and excessive alcohol, are also recommended for individuals at increased risk. These measures complement genetic risk management strategies.
Non-Genetic Factors in Stomach Cancer Development
While genetic predisposition plays a role in a minority of stomach cancer cases, most are sporadic, influenced by various non-genetic factors. One recognized risk factor is infection with Helicobacter pylori (H. pylori) bacteria. Long-term H. pylori infection can cause chronic inflammation and precancerous changes in the stomach lining.
Dietary habits also contribute to stomach cancer risk. Diets high in salted, smoked, or pickled foods, and processed or charcoaled meats, are associated with increased incidence. Conversely, a diet rich in fresh fruits and vegetables may help lower the risk.
Other lifestyle and environmental factors are also linked to stomach cancer. Smoking tobacco significantly increases risk. Excessive alcohol consumption is another contributing factor. Obesity and occupational exposures to chemicals have also been connected to an elevated risk.